ORCID Profile
0000-0002-0500-6984
Current Organisations
Cold Spring Harbor Laboratory
,
The University of Auckland
,
Curtin University
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Publisher: Portland Press Ltd.
Date: 10-03-2015
DOI: 10.1042/CS20140725
Abstract: This study has demonstrated for the first time that cryopreservation of primary immune cells modified their metabolism in a time-dependent fashion, indicated by attenuated aerobic respiration and enhanced glycolytic activity. Measurements were recorded using the Seahorse XFe96 extracellular flux analyser.
Publisher: Hindawi Limited
Date: 2012
DOI: 10.1155/2012/213986
Abstract: In this study we evaluated the onset and resolution of inflammation in control and streptozotocin-induced diabetic rats subjected to a single session of intense exercise. The following measurements were carried out prior to, immediately after, and 2 and 24 hours after exercise: plasma levels of proinflammatory cytokines (TNF- α , IL- 1 β , IL-6, CINC- 2 α / β , MIP-3 α , and IL-6), immunoglobulins (IgA and IgM), acute phase proteins (CRP and C3), and creatine kinase (CK) activity. We also examined the occurrence of macrophage death by measurements of macrophages necrosis (loss of membrane integrity) and DNA fragmentation. An increase was observed in the concentration of IL- 1 β (3.3-fold) and TNF- α (2.0-fold) and in the proportion of necrotic macrophages (4.5-fold) in diabetic rats 24 hours after exercise, while the control group showed basal measurements. Twenty-four hours after the exercise, serum CK activity was elevated in diabetic rats but not in control animals. We concluded that lesion and inflammations resulting from intense exercise were greater and lasted longer in diabetic animals than in nondiabetic control rats.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2007
Publisher: Portland Press Ltd.
Date: 02-1996
DOI: 10.1042/BST024073S
Abstract: In the DSM-IV, in iduals with binge eating disorder (BED) and those with purging disorder (PD) receive a diagnosis of eating disorder not otherwise specified (EDNOS), suggesting no meaningful differences between clinical presentations. This article compares PD and BED on eating disorder severity and comorbid disorders. In iduals with PD (n = 33), DSM-IV BED (n = 23 with BMI >30 kg/m(2) , and n = 18 with BMI between 18.5 and 26.5 kg/m(2) ), and noneating disorder controls (n = 35) completed SCID-I interviews and questionnaires. Eating disorder groups reported significantly greater depression, body dissatisfaction, and dietary restraint and more Axis I disorders compared with controls. Compared with both the obese and normal weight BED groups, PD reported significantly greater dietary restraint and body dissatisfaction. Compared with obese BED, PD reported lower prevalence of impulse control disorders. Findings support differentiating among EDNOS based on behavioral presentation in both research and future nosological schemes such as the DSM-V.
Publisher: Portland Press Ltd.
Date: 08-1998
DOI: 10.1042/BST026S235
Publisher: Wiley
Date: 21-05-2003
DOI: 10.1016/S0014-5793(03)00526-X
Abstract: In pancreatic beta-cells, glutamate has been proposed to mediate insulin secretion as a glucose-derived factor, although it is also considered for its sole catabolic function. Hence, changes in cellular glutamate levels are a matter of debate. Here, we investigated the effects of glucose and the glutamate precursor glutamine on kinetics of glutamate levels together with insulin secretion in INS-1E beta-cells. Preincubation at low (1 mM) glucose resulted in reduced cellular glutamate levels, which were doubled by exposure to glutamine. In glutamine-deprived cells, 5 mM glucose restored glutamate concentrations. Incubation at 15 mM glucose increased cellular glutamate, along with stimulation of insulin secretion, following both glutamine-free and glutamine-rich preincubations. Nuclear magnetic resonance (NMR) spectroscopy of INS-1E cells exposed to 15 mM D-[1-(13)C]glucose revealed glutamate as the major glucose metabolic product. Branched-chain amino acids, such as leucine, reduced cellular glutamate levels at low and intermediate glucose. This study demonstrates that glucose stimulates glutamate generation, whereas branched-chain amino acids promote competitive glutamate expenditure.
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2015
Publisher: Portland Press Ltd.
Date: 15-03-1987
DOI: 10.1042/BJ2420631
Abstract: The concentrations of ATP and the ATP/AMP concentration ratios were maintained in thioglycollate-elicited mouse peritoneal macrophages incubated in vitro for 90 min in the presence or absence of added substrate: rates of glycolysis, lactate formation and glutamine utilization were approximately linear with time for at least 60 min of incubation. The rate of oxygen consumption by macrophages was only increased above the basal rate (i.e. that in the absence of added substrate) by addition of succinate or pyruvate, or by addition of the uncoupling agent carboxyl cyanide m-chlorophenylhydrazone (‘CCCP’) it was decreased by 75% by the addition of KCN. These findings suggest that metabolism of endogenous substrate can provide most, if not all, of the energy requirement of these cells, at least for a short period. The rates of glucose and glutamine utilization by incubated macrophages were approx. 300 and 100 nmol/min per mg of protein respectively. A large proportion of the glutamine that is utilized is converted into glutamate and aspartate, and very little (perhaps less than 10%) is oxidized. Similarly almost all of the glucose that is utilized is converted into lactate and very little is oxidized. This characteristic is similar to that of resting lymphocytes and rapidly iding cells in non-proliferating macrophages it may be a mechanism to provide precision in control of the rate of biosynthetic processes that utilize intermediates of these pathways, e.g. purines and pyrimidines for mRNA for the synthesis of secretory proteins and glycerol 3-phosphate for phospholipid synthesis for membrane recycling. No utilization of acetoacetate or 3-hydroxybutyrate by macrophages was detected. In contrast, both butyrate and oleate were oxidized. The rate of [14C]oleate conversion into 14CO2 (1.3 nmol/h per mg of protein) could account for most of the oxygen consumption by incubated macrophages, suggesting that long-chain fatty acids might provide an important fuel in situ. This may be one explanation for the secretion of lipoprotein lipase by these cells, to provide fatty acids for oxidation from the degradation of local triacylglycerol.
Publisher: Elsevier BV
Date: 03-1995
DOI: 10.1016/0306-3623(94)00177-O
Abstract: 1. This study examines the effect of propionate, normally produced in the gut, on lipid metabolism of resident macrophage. This cell is very abundant in the epithelial lining of the gut. 2. The activity of propionyl-CoA synthetase in macrophages was shown to be 0.39 nmol/min per mg protein, so this cell presents the ability to use propionate. Propionate at concentrations varying from 0.5 to 5 mM did not affect the activities of carnitine acetyltransferase, ATP-citrate lyase, acetoacetyl-CoA thiolase and 3-oxoacid-CoA transferase. 3. Thus this short chain fatty acid did not alter the capacity for transferring acetyl-CoA from mitochondria to cytosol and for ketone bodies formation and oxidation. However, propionate (40 mM) inhibited the incorporation of [1-14C]-palmitate into phospholipids, cholesterol, cholesterol ester and triacylglycerol and the incorporation of [3-14C]-pyruvate into phospholipids. 4. These findings suggest that fibre-rich diet by generating propionate may regulate macrophage lipid metabolism.
Publisher: Wiley
Date: 11-2003
DOI: 10.1007/S11745-003-1174-X
Abstract: FA are known to modulate immune function in conditions such as arthritis and lupus erythematosus. The effects of arachidonic (AA) and oleic acids (OA) on function and pleiotropic gene expression of Raji cells were investigated. The following parameters were evaluated: cytotoxicity as assessed by loss of membrane integrity and DNA fragmentation proliferation as measured by [14C]thymidine incorporation production of interleukin (IL)-10, interferon (INF)-gamma, and tumor necrosis factor (TNF)-alpha and expression of pleiotropic genes by a macroarray technique (83 genes in total). AA was more toxic to Raji cells than OA. Both FA promoted an increase in Raji cell proliferation at 75 microM, whereas OA at high concentrations (200 microM) decreased proliferation. AA reduced the production of IL-10, TNF-alpha, and INF-gamma. On the other hand, OA provoked an increase of INF-gamma production but did not affect the production of IL-10 and TNF-alpha. The proportions of genes with altered expression were 27% for AA and 35% for OA. The FA affected the expression of genes clustered as: cytokines, signal transduction pathways, transcription factors, cell cycle, defense and repair, apoptosis, DNA synthesis, cell adhesion, cytoskeleton, and hormone receptors. The most remarkable changes were observed in the genes of signal transduction pathways. These results led us to conclude that the effect of these FA on B-lymphocytes includes regulation of gene expression. Thus, diets enriched with fat containing OA or AA may affect B lymphocyte function in vivo.
Publisher: Informa UK Limited
Date: 2004
Publisher: Wiley
Date: 18-11-2015
DOI: 10.1113/JP271237
Publisher: Wiley
Date: 03-1996
DOI: 10.1002/CBF.644
Abstract: The present paper examines longitudinally how subjective perceptions about COVID-19, one's community, and the government predict adherence to public health measures to reduce the spread of the virus. Using an international survey (N = 3040), we test how infection risk perception, trust in the governmental response and communications about COVID-19, conspiracy beliefs, social norms on distancing, tightness of culture, and community punishment predict various containment-related attitudes and behavior. Autoregressive analyses indicate that, at the personal level, personal hygiene behavior was predicted by personal infection risk perception. At social level, social distancing behaviors such as abstaining from face-to-face contact were predicted by perceived social norms. Support for behavioral mandates was predicted by confidence in the government and cultural tightness, whereas support for anti-lockdown protests was predicted by (lower) perceived clarity of communication about the virus. Results are discussed in light of policy implications and creating effective interventions.
Publisher: Springer Science and Business Media LLC
Date: 04-01-2012
Publisher: Elsevier BV
Date: 03-1999
DOI: 10.1016/S0006-2952(98)00311-6
Abstract: The membrane spanning complement channel is assumed to be a nonselective ion 'pore', although little evidence is available to support this hypothesis. In this paper we provide evidence that Ca2+ entry and Cl- exit occur rapidly after complement activation and precede the development of a long-lasting complement-dependent inward current. Addition of rabbit serum (a source of heterologous complement) and mouse anti-human insulin receptor antibody to a single Xenopus oocyte expressing human insulin receptor was shown to stimulate an initial hyperpolarising current followed by a sustained depolarising current. On voltage cl ing the oocyte, a novel long-lasting inward current generated by serum addition was detected. Complement classical pathway-stimulated calcium influx into the oocyte was directly demonstrated using 45Ca influx measurements. In addition, we found that Ca2+ influx was required for the stimulation of the complement alternative pathway-dependent inward current. The novel conductance elicited by the classical pathway was outwardly rectifying, had a reversal potential of -35 +/- 8 mV (or -52 +/- 7 mV in the presence of chloride channel inhibitors), was inhibited by nifedipine, and was observed in the presence but not in the absence of the pore-forming complement component C9. As overactivation of complement does play a role in many inflammatory or autoimmune diseases, inhibition of early complement-mediated ion flux might restrict tissue damage and aid recovery from such diseases.
Publisher: Portland Press Ltd.
Date: 02-1996
DOI: 10.1042/BST024074S
Abstract: The global COVID-19 pandemic has brought numerous challenges for conducting the human subjects research needed to advance science and improve health. The purpose of this article is to discuss how a college of nursing at a large public university in the southeast United States has responded to the challenges of conducting research during the novel COVID-19 pandemic. Seven faculty researchers at the University of South Carolina College of Nursing share their experiences in overcoming the unique challenges of conducting research because of the COVID-19 pandemic. Strategies to overcome the challenges posed by COVID-19 are presented within the context of the research process, career implications, communication, and maintaining morale. Fears of COVID-19 and social distancing measures have hindered participant recruitment, enrollment, and involvement in ongoing studies. Increasing virtual technology use and enhancing safety precautions have assisted researchers to overcome barriers. Scholarly writing has increased for some faculty members whose studies have been stalled by the pandemic, yet others have seen a decline because of additional personal responsibilities. The careers of faculty members across all ranks have been uniquely affected by the pandemic. With most faculty working remotely, enhanced communication strategies at the university and college have supported the research enterprise. Morale has been adversely affected, but a variety of personal and collegial efforts have helped faculty cope and preserve a sense of normalcy during this devastating pandemic. Faculty and their ability to conduct the research needed to inform clinical and public health practice have been adversely affected by the COVID-19 pandemic. Despite the challenges of conducting research during this unprecedented crisis, faculty and institutions are taking novel steps to ensure the continuity of scientific progress for improving the health and well-being of patients and populations.
Publisher: Portland Press Ltd.
Date: 18-02-2005
DOI: 10.1042/CS20040290
Abstract: Specific amino acids are now known to acutely and chronically regulate insulin secretion from pancreatic β-cells in vivo and in vitro. Understanding the molecular mechanisms by which amino acids regulate insulin secretion may identify novel targets for future diabetes therapies. Mitochondrial metabolism is crucial for the coupling of amino acid and glucose recognition to the exocytosis of the insulin granules. This is illustrated by in vitro and in vivo observations discussed in the present review. Mitochondria generate ATP, which is the main coupling factor in insulin secretion however, the subsequent Ca2+ signal in the cytosol is necessary, but not sufficient, for full development of sustained insulin secretion. Hence mitochondria generate ATP and other coupling factors serving as fuel sensors for the control of the exocytotic process. Numerous studies have sought to identify the factors that mediate the lifying pathway over the Ca2+ signal in nutrient-stimulated insulin secretion. Predominantly, these factors are nucleotides (GTP, ATP, cAMP and NADPH), although metabolites have also been proposed, such as long-chain acyl-CoA derivatives and the key amino acid glutamate. This scenario highlights further the importance of the key enzymes or transporters, glutamate dehydrogenase, the aspartate and alanine aminotransferases and the malate/aspartate shuttle, in the control of insulin secretion. Therefore amino acids may play a direct or indirect (via generation of putative messengers of mitochondrial origin) role in insulin secretion.
Publisher: Wiley
Date: 03-1996
DOI: 10.1002/(SICI)1099-0844(199603)14:1<1::AID-CBF644>3.3.CO;2-Z
Publisher: Portland Press Ltd.
Date: 23-11-2009
DOI: 10.1042/CS20090433
Abstract: It is now widely accepted that hypertension and endothelial dysfunction are associated with an insulin-resistant state and thus with the development of T2DM (Type 2 diabetes mellitus). Insulin signalling is impaired in target cells and tissues, indicating that common molecular signals are involved. The free radical NO• regulates cell metabolism, insulin signalling and secretion, vascular tone, neurotransmission and immune system function. NO• synthesis is essential for vasodilation, the maintenance of blood pressure and glucose uptake and, thus, if levels of NO• are decreased, insulin resistance and hypertension will result. Decreased blood levels of insulin, increased AngII (angiotensin II), hyperhomocysteinaemia, increased ADMA (asymmetric ω-NG,NG-dimethylarginine) and low plasma L-arginine are all conditions likely to decrease NO• production and which are associated with diabetes and cardiovascular disease. We suggest in the present article that the widely reported beneficial effects of exercise in the improvement of metabolic and cardiovascular health are mediated by enhancing the flux of muscle- and kidney-derived amino acids to pancreatic and vascular endothelial cells aiding the intracellular production of NO•, therefore resulting in normalization of insulin secretion, vascular tone and insulin sensitivity. Exercise may also have an impact on AngII and ADMA signalling and the production of pro- and anti-inflammatory cytokines in muscle, so reducing the progression and development of vascular disease and diabetes. NO• synthesis will be increased during exercise in the vascular endothelial cells so promoting blood flow. We suggest that exercise may promote improvements in health due to positive metabolic and cytokine-mediated effects.
Publisher: MDPI AG
Date: 28-03-2021
DOI: 10.3390/NU13041110
Abstract: Aging is associated with impairment in skeletal muscle mass and contractile function, predisposing to fat mass gain, insulin resistance and diabetes. The impact of Vitamin D (VitD) supplementation on skeletal muscle mass and function in older adults is still controversial. The aim of this review was to summarize data from randomized clinical trials, animal dietary intervention and cell studies in order to clarify current knowledge on the effects of VitD on skeletal muscle as reported for these three types of experiments. A structured research of the literature in Medline via PubMed was conducted and a total of 43 articles were analysed (cells n = 18, animals n = 13 and humans n = 13). The results as described by these key studies demonstrate, overall, at cell and animal levels, that VitD treatments had positive effects on the development of muscle fibres in cells in culture, skeletal muscle force and hypertrophy. Vitamin D supplementation appears to regulate not only lipid and mitochondrial muscle metabolism but also to have a direct effect on glucose metabolism and insulin driven signalling. However, considering the human perspective, results revealed a predominance of null effects of the vitamin on muscle in the ageing population, but experimental design may have influenced the study outcome in humans. Well-designed long duration double-blinded trials, standardised VitD dosing regimen, larger s le sized studies and standardised measurements may be helpful tools to accurately determine results and compare to those observed in cells and animal dietary intervention models.
Publisher: Portland Press Ltd.
Date: 06-1987
DOI: 10.1042/BST0150536
Publisher: Elsevier BV
Date: 06-2008
DOI: 10.1016/J.DIABRES.2007.12.009
Abstract: The purpose of this study was to determine if immune mechanisms in GAD positive patients' contribute to the pathogenesis of a specific sub-type of Type 2 diabetes. GAD positive (n=8) and GAD negative (n=8) subjects diagnosed with Type 2 diabetes were matched for age, gender, body mass index, duration of diabetes and glycaemic control. All subjects underwent an insulin-modified frequently s led intravenous glucose tolerance test to measure insulin sensitivity and insulin secretory function with minimal model analysis. In addition, BRIN-BD11 clonal beta-cells were supplemented with patients' sera to determine basal and alanine-stimulated insulin secretion and terminal complement complex (TCC) formation. Both groups were severely insulin resistant (0.56+/-0.17 vs. 0.99+/-0.3310(-4)min(-1)/(microUml(-1)) for GADneg and GADpos, respectively) but the GAD negative subjects had a higher basal (87+/-11 vs. 58+/-14pmoll(-1), p<0.05) and glucose-stimulated insulin secretion (DeltaAUCins 0.96+/-0.12 vs. 0.60+/-0.12pmol/(l(-1)min), p<0.05). In vivo measures of insulin secretion were negatively correlated with TCC formation, independent of antibody status. In conclusion, GAD positive subjects initially diagnosed with Type 2 diabetes are unable to compensate for insulin resistance due to more pronounced beta-cell impairment. TCC formation may be partly responsible for the insulin secretory dysfunction associated with this specific sub-type of Type 2 diabetes.
Publisher: Portland Press Ltd.
Date: 13-12-2001
DOI: 10.1042/CS1000091
Abstract: Soluble forms of intercellular adhesion molecule-1, vascular cell adhesion molecule-1 and E-selectin (termed sICAM-1, sVCAM-1 and sE-selectin respectively) are found in the plasma, and are elevated during inflammatory conditions in which there is increased expression of the cellular forms of the molecules on endothelial and other cells. sICAM-1, sVCAM-1 and sE-selectin concentrations were measured in the plasma of 140 healthy Caucasian subjects aged between 18 and 75 years (100 males/40 females). sICAM-1 concentrations varied between 59.9 and 299.7 ng/ml (median 150 ng/ml), sVCAM-1 concentrations varied between 222.8 and 1672.9 ng/ml (median 662 ng/ml) and sE-selectin concentrations varied between 12.4 and 90.3 ng/ml (median 45.5 ng/ml). There were significant positive linear correlations between age and the plasma concentrations of sICAM-1 (r = 0.580 P 0.001) and sVCAM-1 (r = 0.392 P 0.001), which were retained when the effects of gender, body mass index and fasting plasma triacylglycerol and total cholesterol concentrations were controlled for. The significant positive linear correlation between age and the plasma concentration of sE-selectin (r = 0.234 P = 0.027) was lost when other variables were controlled for. Male subjects 40 years of age had significantly lower plasma concentrations of both sICAM-1 and sVCAM-1 than males 55 years of age (both P 0.001), but the difference in plasma sE-selectin concentrations between the age groups did not reach significance (P = 0.073). Subgroups of 16 males aged 40 years and 12 elderly subjects ( 55 years of age) participated in a doubled-blind, placebo-controlled study of fish oil supplementation over 12 weeks. The level of eicosapentaenoic acid in plasma phospholipids did not change with placebo supplementation, but was significantly increased with fish oil supplementation in both young male and elderly subjects (median increase 200%). sICAM-1, sVCAM-1 and sE-selectin concentrations were unaffected by supplementation with placebo in either young male or elderly subjects. sICAM-1 concentrations were unaffected by fish oil supplementation. sE-selectin concentrations were significantly increased by fish oil supplementation in young males (P = 0.043 median increase 38%), but fish oil tended to decrease plasma sE-selectin concentrations in the elderly subjects (P = 0.075), with a median decrease of 11%. sVCAM-1 concentrations were unaffected by fish oil supplementation in young males. Fish oil supplementation significantly decreased plasma sVCAM-1 concentrations in the elderly subjects (P = 0.043), with a median decrease of 20% (range 16–60%). These observations suggest that fish oil decreases endothelial activation in elderly subjects.
Publisher: Wiley
Date: 10-04-2016
DOI: 10.1113/JP271858
Publisher: Portland Press Ltd.
Date: 08-1996
DOI: 10.1042/BST024463S
Publisher: Springer Science and Business Media LLC
Date: 12-09-2010
DOI: 10.1038/NI.1935
Publisher: Elsevier BV
Date: 06-2015
Publisher: Proceedings of the National Academy of Sciences
Date: 03-04-2023
Abstract: The alarming rise in superbugs that are resistant to drugs of last resort, including vancomycin-resistant enterococci and staphylococci, has become a significant global health hazard. Here, we report the click chemistry synthesis of an unprecedented class of shapeshifting vancomycin dimers (SVDs) that display potent activity against bacteria that are resistant to the parent drug, including the ESKAPE pathogens, vancomycin-resistant Enterococcus (VRE), methicillin-resistant Staphylococcus aureus (MRSA), as well as vancomycin-resistant S. aureus (VRSA). The shapeshifting modality of the dimers is powered by a triazole-linked bullvalene core, exploiting the dynamic covalent rearrangements of the fluxional carbon cage and creating ligands with the capacity to inhibit bacterial cell wall biosynthesis. The new shapeshifting antibiotics are not disadvantaged by the common mechanism of vancomycin resistance resulting from the alteration of the C-terminal dipeptide with the corresponding d -Ala- d -Lac depsipeptide. Further, evidence suggests that the shapeshifting ligands destabilize the complex formed between the flippase MurJ and lipid II, implying the potential for a new mode of action for polyvalent glycopeptides. The SVDs show little propensity for acquired resistance by enterococci, suggesting that this new class of shapeshifting antibiotic will display durable antimicrobial activity not prone to rapidly acquired clinical resistance.
Publisher: Springer Science and Business Media LLC
Date: 12-2015
Publisher: Portland Press Ltd.
Date: 08-1997
DOI: 10.1042/BST025403S
Abstract: We assessed the influence of systemic lidocaine administration on ventilatory and circulatory parameters, and the pneumoperitoneum impact on the cardiopulmonary system during a laparoscopic appendectomy in children. A single-center parallel single-masked randomized controlled study was carried out with 58 patients (3-17 years). Intravenous lidocaine bolus of 1.5 mg/kg over 5 min before induction of anesthesia followed by lidocaine infusion at 1.5 mg/kg/h intraoperatively. Respiratory system compliance (C, C/kg), P
Publisher: Portland Press Ltd.
Date: 28-04-1999
DOI: 10.1042/CS0960549
Abstract: Despite the large body of information on the role of corticosteroids in regulating lymphocyte and phagocyte function, the role of the hormone adrenaline in immunoregulation is an under-investigated topic. The present study has addressed the effects of adrenaline on the rates of utilization and oxidation of glucose and glutamine, the phagocytic capacity and the rate of superoxide production by rat neutrophils. Incubation of rat neutrophils in the presence of 50 µM adrenaline caused a marked elevation in glucose metabolism, an effect that could be blocked by propranolol. Adrenaline caused a partial inhibition of glutamine utilization by neutrophils, an effect that was also blocked by propranolol. These effects of adrenaline could be mimicked by 100 µM dibutyryl cAMP. Phosphate-dependent glutaminase activity was significantly elevated in neutrophils incubated in the presence of 50 µM adrenaline or 100 µM dibutyryl cAMP for 1 h, whereas glutamine oxidation was significantly depressed (P 0.05) under these conditions. The elevation in enzyme activity was only partially blocked by propranolol. The phagocytic activity of rat neutrophils was not altered by adrenaline in the presence of either glucose or glutamine. The rate of phorbol 12-myristate 13-acetate-induced superoxide production in the presence of glucose was potently reduced by the addition of 5 nM or 50 µM adrenaline. This effect could be mimicked by dibutyryl cAMP. However, when rat neutrophils were incubated in the presence of glutamine plus adrenaline (5 nM or 50 µM), the rate of superoxide production was only marginally reduced. These findings support the proposition that adrenaline may deviate the flux of glucose from the NADPH-producing pentose phosphate pathway, thus reducing substrate availability for the superoxide-generating NADPH oxidase. However, glutamine metabolism may still give rise to substantial quantities of NADPH from the glutaminolysis pathway. We postulate that glutamine metabolism may thus provide a protective mechanism against the inhibitory effect of adrenaline on superoxide production by neutrophils.
Publisher: Portland Press Ltd.
Date: 10-2001
DOI: 10.1042/BST029A116A
Publisher: MDPI AG
Date: 12-10-2020
DOI: 10.3390/NU12103111
Abstract: Supplementation with the most efficient form of Vitamin D (VitD3) results in improvements in energy metabolism, muscle mass and strength in VitD deficient in iduals. Whether similar outcomes occur in VitD sufficient in iduals’ remains to be elucidated. The aim of this study is to determine the effect of VitD3 supplementation on resting metabolic rate (RMR), body composition and strength in VitD sufficient physically active young adults. Participants completed pre-supplementation testing before being matched for sunlight exposure and randomly allocated in a counterbalanced manner to the VitD3 or placebo group. Following 12 weeks of 50 IU/kg body-mass VitD3 supplementation, participants repeated the pre-supplementation testing. Thirty-one adults completed the study (19 females and 12 males mean ± standard deviation (SD) age = 26.6 ± 4.9 years BMI = 24.2 ± 4.1 kg·m2). The VitD group increased serum total 25(OH)D by 30 nmol/L while the placebo group decreased total serum concentration by 21 nmol/L, reaching 123 (51) and 53 (42.2) nmol/L, respectively. There were no significant changes in muscle strength or power, resting metabolic rate and body composition over the 12-week period. Physically active young adults that are VitD sufficient have demonstrated that no additional physiological effects of achieving supraphysiological serum total 25(OH)D concentrations after VitD3 supplementation.
Publisher: Springer Science and Business Media LLC
Date: 23-06-2021
DOI: 10.1038/S41430-021-00960-Z
Abstract: Various nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of erse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.
Publisher: Elsevier
Date: 2016
Publisher: Springer Science and Business Media LLC
Date: 2011
Publisher: Portland Press Ltd.
Date: 11-1996
DOI: 10.1042/BST024619SB
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/105828
Abstract: Type 2 diabetes (T2DM), Alzheimer’s disease (AD), and insulin resistance are age-related conditions and increased prevalence is of public concern. Recent research has provided evidence that insulin resistance and impaired insulin signalling may be a contributory factor to the progression of diabetes, dementia, and other neurological disorders. Alzheimer’s disease (AD) is the most common subtype of dementia. Reduced release (for T2DM) and decreased action of insulin are central to the development and progression of both T2DM and AD. A literature search was conducted to identify molecular commonalities between obesity, diabetes, and AD. Insulin resistance affects many tissues and organs, either through impaired insulin signalling or through aberrant changes in both glucose and lipid (cholesterol and triacylglycerol) metabolism and concentrations in the blood. Although epidemiological and biological evidence has highlighted an increased incidence of cognitive decline and AD in patients with T2DM, the common molecular basis of cell and tissue dysfunction is rapidly gaining recognition. As a cause or consequence, the chronic inflammatory response and oxidative stress associated with T2DM, amyloid- β (A β ) protein accumulation, and mitochondrial dysfunction link T2DM and AD.
Publisher: Wiley
Date: 12-02-2014
DOI: 10.1113/EXPPHYSIOL.2013.077495
Abstract: Recent metabolic profiling studies have identified a correlation between branched-chain amino acid levels, insulin resistance associated with prediabetes and susceptibility to type 2 diabetes. Glucose and lipids in chronic excess have been reported to induce toxic effects in pancreatic β-cells, but the effect of elevated amino acid concentrations on primary islet cell function has not been investigated to date. The aim of this study was to investigate the effect of chronic exposure to various amino acids on islet cell function in vitro. Isolated rat islets were incubated over periods of 48 h with a range of concentrations of in idual amino acids (0.1 μm to 10 mm). After 48 h, islets were assessed for glucose-dependent insulin secretion capacity, proliferation or islet cell apoptosis. We report that elevated levels of branched-chain amino acids have little effect on pancreatic islet cell function or viability however, increased levels of the amino acid l-arginine were found to be β-cell toxic, causing a dose-dependent decrease in insulin secretion accompanied by a decrease in islet cell proliferation and an increase in islet cell apoptosis. These effects were not due to l-arginine-dependent increases in production of nitric oxide but arose through elicitation of the islet cell endoplasmic reticulum stress response. This novel finding indicates, for the first time, that the l-arginine concentration in vitro may impact negatively on islet cell function, thus indicating further complexity in relationship to in vivo susceptibility of β-cells to nutrient-induced dysfunction.
Publisher: Portland Press Ltd.
Date: 08-2002
DOI: 10.1042/CS20010259
Publisher: MDPI AG
Date: 07-12-2022
Abstract: In animal studies, HDAC inhibitors such as butyrate have been reported to reduce plasma cholesterol, while conferring protection from diabetes, but studies on the underlying mechanisms are lacking. This study compares the influence of butyrate and other HDAC inhibitors to that of statins on cholesterol metabolism in multiple cell lines, but primarily in HepG2 hepatic cells due to the importance of the liver in cholesterol metabolism. Sodium butyrate reduced HepG2 cholesterol content, as did sodium valproate and the potent HDAC inhibitor trichostatin A, suggesting HDAC inhibition as the exacting mechanism. In contrast to statins, which increase SREBP-2 regulated processes, HDAC inhibition downregulated SREBP-2 targets such as HMGCR and the LDL receptor. Moreover, in contrast to statin treatment, butyrate did not increase cholesterol uptake by HepG2 cells, consistent with its failure to increase LDL receptor expression. Sodium butyrate also reduced ABCA1 and SRB1 protein expression in HepG2 cells, but these effects were not consistent across all cell types. Overall, the underlying mechanism of cell cholesterol lowering by sodium butyrate and HDAC inhibition is consistent with impaired SREBP-2 signalling, and calls into question the possible use of butyrate for lowering of serum LDL cholesterol in humans.
Publisher: Public Library of Science (PLoS)
Date: 08-03-2013
Publisher: Portland Press Ltd.
Date: 10-2000
DOI: 10.1042/BST028A255B
Publisher: Portland Press Ltd.
Date: 07-1989
DOI: 10.1042/BJ2610211
Abstract: 1. The metabolism of mouse thioglycollate-elicited peritoneal macrophages was studied in culture for up to 96 h. 2. The rates of glycolysis, lactate formation and glutamine utilization were approximately linear with time for at least 80 h of culture. 3. The rates of glucose and glutamine utilization by cultured macrophages were approx. 500 and 90 nmol/h per mg of protein respectively. This rate of glucose utilization is at least 50% greater than that previously reported for macrophages during 60 min incubation in a shaking flask and it is now increased by addition of glutamine to the culture medium. The rate of glutamine utilization in culture is similar to that previously reported for macrophages during 60 min incubation. The major end-product of glucose metabolism is lactate, and those of glutamine metabolism are CO2, glutamate, ammonia and alanine. 4. Oleate was utilized by these cells: 14C from [14C]oleate was incorporated into CO2 and cellular lipid. The highest rate of oleate utilization was observed when both glucose and glutamine were present in the culture medium. The presence of oleate in the culture medium did not affect the rates of utilization of either glucose or glutamine. Of the [14C]oleate incorporated into lipid, approx. 80% was incorporated into triacylglycerol and only 18% into phospholipid. 5. The turnover rate for the total ATP content of the macrophage in culture is about 10 times per minute: the value for the perfused isolated maximally working rat heart is 22. This indicates a high metabolic rate for macrophages, and consequently emphasizes the importance of the provision of fuels for their function in an immune response.
Publisher: Portland Press Ltd.
Date: 02-1996
DOI: 10.1042/BST024072S
Publisher: Wiley
Date: 2005
DOI: 10.1002/CBF.1291
Publisher: Portland Press Ltd.
Date: 17-07-2002
DOI: 10.1042/CS1030179
Abstract: Neutrophils are phagocytic cells of the innate immune system that use a combination of reactive oxygen species and anti-microbial toxins to kill and destroy ingested micro-organisms. Once they have performed their function, neutrophils die by apoptosis, which is important for the effective resolution of the inflammatory response. Both glucose and glutamine are important fuels for neutrophils, yet little has been done to investigate the comparative effects of glucose and glutamine on neutrophil apoptosis. We hypothesized that glucose and/or glutamine significantly alter rates of spontaneous and anti-Fas antibody-induced apoptosis of human neutrophils cultured ex vivo. Neutrophil apoptosis was reduced by increasing the extracellular concentration of glucose, but was unaffected by glutamine concentration. The protective effect of glucose appeared to correlate with the rate of glucose utilization. The addition of a competitive inhibitor of glycolysis, 2-deoxy-d-glucose (10mM), attenuated the protective effect of 5.5mM glucose, indicating that glucose metabolism is essential for its protective effect against apoptosis. There was a significant (P .05) reduction in the intracellular ATP concentration of neutrophils incubated in the absence of extracellular glucose compared with cells incubated in the presence of 5.5mM glucose. The protective effect of glucose against apoptosis may be mediated by maintenance of the intracellular ATP concentration.
Publisher: Portland Press Ltd.
Date: 08-1997
DOI: 10.1042/BST025404S
Abstract: Ornamental crabapple is an important woody ornamental plant in the Northern Hemisphere. Its flowers, fruits, leaves and tree habit are all important ornamental characters. As there has been no research on the selection of superior parents and phenotypic variation, new varieties of ornamental crabapple are mainly selected from open-pollination progeny. In order to explore the transmission rule of ornamental traits between parents and offspring of crabapple, and to provide a basis for the selection of hybrid parents for directional breeding, 14 pairs of SSR markers were used in this study for paternity analysis of 384 offspring from 4 female parents crossed with 91 candidate male parents. And 273 offspring (71.1%) were matched with only the father at a 95% strict confidence level. We reconstructed 7 full-sib families (number of progeny ≥ 10) on the basis of the paternity analysis results. Genetic analysis of characters in the full-sib families revealed that green leaves and white flowers were dominant traits. All the hybrid offspring from the white flower (♀) × non-white flower (♂) cross produced white flowers, while 7.04% produced non-white flowers when both parents had white flowers. The results showed that white flowers might be a dominant qualitative trait in crabapple, while the depth of red was a quantitative trait. The genetic characteristics of green and non-green leaves and the depth of red of the peel were similar to flower color. Compared with the upright and spreading traits, the weeping trait was recessive. Some progeny showed an earlier blooming period, indicating the possibility of breeding for blooming period. Our findings are important for parent screening and improving the breeding efficiency of new varieties in ornamental crabapple hybridization.
Publisher: Elsevier BV
Date: 09-2007
Publisher: Springer Science and Business Media LLC
Date: 21-04-2022
DOI: 10.1186/S40798-022-00445-8
Abstract: Reverse periodization is commonly touted as a salient planning strategy to improve sport performance in athletes, but benefits have not been clearly described. We sought to identify the main characteristics of reverse periodization, and the influence of training volume and periodization models on enhancing physiological measures and sports performance. Systematic review. The electronic databases Scopus, PubMed and Web of Science were searched using a comprehensive list of relevant terms. A total of 925 studies were identified, and after removal of duplicates and studies based on title and abstract screening, 17 studies remained, and 11 finally included in the systematic review. There was a total of 200 athletes in the included studies. Reverse periodization does not provide superior performance improvements in swimming, running, muscular endurance, maximum strength, or maximal oxygen uptake, compared to traditional or block periodization. The quality of evidence levels for the reverse periodization studies was 1b (in idual randomized controlled trial) for two investigations, 2b (in idual cohort study) for the remaining studies and a mean of 4.9 points in the PEDro scale (range 0–7). It appears that reverse periodization is no more effective than other forms of periodization in improving sports performance. More comparative studies on this alternative version of periodization are required to verify its effectiveness and utility across a range of endurance sports.
Publisher: Portland Press Ltd.
Date: 05-1997
DOI: 10.1042/BST025319S
Abstract: SignificanceSmall modular reactors (SMRs), proposed as the future of nuclear energy, have purported cost and safety advantages over existing gigawatt-scale light water reactors (LWRs). However, few studies have assessed the implications of SMRs for the back end of the nuclear fuel cycle. The low-, intermediate-, and high-level waste stream characterization presented here reveals that SMRs will produce more voluminous and chemically hysically reactive waste than LWRs, which will impact options for the management and disposal of this waste. Although the analysis focuses on only three of dozens of proposed SMR designs, the intrinsically higher neutron leakage associated with SMRs suggests that most designs are inferior to LWRs with respect to the generation, management, and final disposal of key radionuclides in nuclear waste.
Publisher: Elsevier BV
Date: 2006
Publisher: Wiley
Date: 09-2004
DOI: 10.1007/S11745-004-1307-2
Abstract: The effects of EPA and DHA on the function and gene expression of a B-lymphocyte cell line (Raji) were investigated. Proliferation production of interleukin-10 (IL-10), tumor necrosis factor (TNF)-alpha, and interferon (INF)-gamma and expression of pleiotropic genes were evaluated. Cell proliferation was increased in the presence of 12.5 microM EPA (approximately twofold) and 12.5 microM DHA (approximately 1.5-fold). EPA and DHA (25 microM) also decreased production of the key immunoregulatory cytokines IL-10, TNF-alpha, and INF-gamma. EPA and DHA changed the expression of specific genes, but this effect was more marked for EPA (25.9% of genes investigated) compared with DHA (8.4% of genes investigated). EPA and DHA affected the expression of genes clustered as: cytokines, signal transduction, transcription, cell cycle, defense and repair, apoptosis, cell adhesion, cytoskeleton, and hormones. The most remarkable changes were observed in the genes of signal transduction and transcription. These results led us to conclude that the mechanism of DHA and EPA effects on B-lymphocyte functions includes regulation of gene expression. Thus, the ingestion of fish oil, a rich source of EPA and DHA, may have a strong effect on B-lymphocyte function in vivo. However, remarkable differences were observed between DHA and EPA, demonstrating that specific effects of these FA may be responsible for the marked differences in edible oil effects on immune function in vivo reported by others.
Publisher: Public Library of Science (PLoS)
Date: 03-11-2015
Publisher: Elsevier BV
Date: 11-1997
DOI: 10.1016/S0006-2952(97)00266-9
Abstract: The complement cascade is an important component in many immune and inflammatory reactions and may contribute to both the diarrhoea and inflammation associated with inflammatory bowel disease. Isolated rat colonic mucosae were voltage cl ed in Ussing chambers. Basolateral addition of zymosan-activated whole human serum (ZAS) induced a rapid onset, transient inward short circuit current (SCC). This response was concentration dependent and was significantly attenuated by pre-heating ZAS at 60 degrees C for 30 min. Depletion of complement from normal human serum with cobra venom factor (CVF) significantly lowered SCC responses. Chloride was the primary charge carrying ion as responses to ZAS were abolished in the presence of the loop diuretic bumetanide. The complement component C3a stimulated ion transport but not to the same extent as whole serum. Exogenous C5 was without effect. The cyclooxygenase inhibitor piroxicam significantly attenuated the response to ZAS. These findings support the possibility that complement activation may contribute to the pathophysiology of secretory diarrhoea since activation of electrogenic chloride secretion converts intestinal epithelia to a state of net fluid secretion.
Publisher: Springer Berlin Heidelberg
Date: 2014
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 07-2013
Publisher: Portland Press Ltd.
Date: 15-03-2011
DOI: 10.1042/BJ20100655
Abstract: Insulin secretion from pancreatic β-cells is controlled by complex metabolic and energetic changes provoked by exposure to metabolic fuels. Perturbations in these processes lead to impaired insulin secretion, the ultimate cause of T2D (Type 2 diabetes). To increase our understanding of stimulus–secretion coupling and metabolic processes potentially involved in the pathogenesis of T2D, a comprehensive investigation of the metabolic response in the glucose-responsive INS-1 832/13 and glucose-unresponsive INS-1 832/2 β-cell lines was performed. For this metabolomics analysis, we used GC/MS (gas chromatography/mass spectrometry) combined with multivariate statistics. We found that perturbed secretion in the 832/2 line was characterized by disturbed coupling of glycolytic and TCA (tricarboxylic acid)-cycle metabolism. The importance of this metabolic coupling was reinforced by our observation that insulin secretion partially could be reinstated by stimulation of the cells with mitochondrial fuels which bypass glycolytic metabolism. Furthermore, metabolic and functional profiling of additional β-cell lines (INS-1, INS-1 832/1) confirmed the important role of coupled glycolytic and TCA-cycle metabolism in stimulus–secretion coupling. Dependence of the unresponsive clones on glycolytic metabolism was paralleled by increased stabilization of HIF-1α (hypoxia-inducible factor 1α). The relevance of a similar perturbation for human T2D was suggested by increased expression of HIF-1α target genes in islets from T2D patients.
Publisher: Portland Press Ltd.
Date: 15-01-2009
DOI: 10.1042/CS20080138
Abstract: Acute insulin-releasing actions of amino acids have been studied in detail, but comparatively little is known about the β-cell effects of long-term exposure to amino acids. The present study examined the effects of prolonged exposure of β-cells to the metabolizable amino acid L-alanine. Basal insulin release or cellular insulin content were not significantly altered by alanine culture, but acute alanine-induced insulin secretion was suppressed by 74% (P& .001). Acute stimulation of insulin secretion with glucose, KCl or KIC (2-oxoisocaproic acid) following alanine culture was not affected. Acute alanine exposure evoked strong cellular depolarization after control culture, whereas AUC (area under the curve) analysis revealed significant (P& .01) suppression of this action after culture with alanine. Compared with control cells, prior exposure to alanine also markedly decreased (P& .01) the acute elevation of [Ca2+]i (intracellular [Ca2+]) induced by acute alanine exposure. These diminished stimulatory responses were partially restored after 18 h of culture in the absence of alanine, indicating reversible amino-acid-induced desensitization. 13C NMR spectra revealed that alanine culture increased glutamate labelling at position C4 (by 60% P& .01), as a result of an increase in the singlet peak, indicating increased flux through pyruvate dehydrogenase. Consistent with this, protein expression of the pyruvate dehydrogenase kinases PDK2 and PDK4 was significantly reduced. This was accompanied by a decrease in cellular ATP (P& .05), consistent with diminished insulin-releasing actions of this amino acid. Collectively, these results illustrate the phenomenon of β-cell desensitization by amino acids, indicating that prolonged exposure to alanine can induce reversible alterations to metabolic flux, Ca2+ handling and insulin secretion.
Publisher: Portland Press Ltd.
Date: 1999
DOI: 10.1042/CS19980187
Publisher: Portland Press Ltd.
Date: 02-1996
DOI: 10.1042/BST024150S
Abstract: Optical-resolution photoacoustic microscopy (OR-PAM) can provide functional, anatomical, and molecular images at micrometer level resolution with an imaging depth of less than 1 mm in tissue. However, the imaging speed of traditional OR-PAM is often low due to the point-by-point mechanical scanning and cannot capture time-sensitive dynamic information. In this work, we demonstrate a recent effort in improving the imaging speed of OR-PAM, using a newly developed water-immersible two-axis scanner. Driven by water-compatible electromagnetic actuation force, the new scanning mirror employs a novel torsion-bending mechanism to achieve fast 2D scanning. The torsion scanning along the fast-axis works in the resonant model, and the bending scanning along the slow-axis operate at the quasi-static mode. The scanning speed and scanning range along the two axes can be independently adjusted. Steered by the two-axis torsion-bending scanning mirror immersed in water, the focused excitation light and the generated acoustic wave can be confocally aligned over the entire imaging area. Thus, a high imaging speed can be achieved without sacrificing the detection sensitivity. Equipped with the torsion-bending scanner, the high-speed OR-PAM system has achieved a cross-sectional frame rate of 400 Hz, and a volumetric imaging speed of 1 Hz over a field of view of 1.5 × 2.5 mm
Publisher: Portland Press Ltd.
Date: 06-1999
DOI: 10.1042/CS19980340
Publisher: Portland Press Ltd.
Date: 27-09-2010
DOI: 10.1042/BSR20090138
Abstract: Various pancreatic β-cell stressors including cytokines and saturated fatty acids are known to induce oxidative stress, which results in metabolic disturbances and a reduction in insulin secretion. However, the key mechanisms underlying dysfunction are unknown. We investigated the effects of prolonged exposure (24 h) to pro-inflammatory cytokines, H2O2 or PA (palmitic acid) on β-cell insulin secretion, ATP, the NADPH oxidase (nicotinamide adenine dinucleotide phosphate oxidase) component p47phox and iNOS (inducible nitric oxide synthase) levels using primary mouse islets or clonal rat BRIN-BD11 β-cells. Addition of a pro-inflammatory cytokine mixture [IL-1β (interleukin-1β), TNF-α (tumour necrosis factor-α) and IFN-γ (interferon-γ)] or H2O2 (at sub-lethal concentrations) inhibited chronic (24 h) levels of insulin release by at least 50% (from islets and BRIN-BD11 cells), while addition of the saturated fatty acid palmitate inhibited acute (20 min) stimulated levels of insulin release from mouse islets. H2O2 decreased ATP levels in the cell line, but elevated p47phox and iNOS levels as did cytokine addition. Similar effects were observed in mouse islets with respect to elevation of p47phox and iNOS levels. Addition of antioxidants SOD (superoxide dismutase), Cat (catalase) and NAC (N-acetylcysteine) attenuated H2O2 or the saturated fatty acid palmitate-dependent effects, but not cytokine-induced dysfunction. However, specific chemical inhibitors of NADPH oxidase and/or iNOS appear to significantly attenuate the effects of cytokines, H2O2 or fatty acids in islets. While pro-inflammatory cytokines are known to increase p47phox and iNOS levels in β-cells, we now report that H2O2 can increase levels of the latter two proteins, suggesting a key role for positive-feedback redox sensitive regulation of β-cell dysfunction.
Publisher: Elsevier BV
Date: 07-1986
DOI: 10.1016/S0006-291X(86)80551-4
Abstract: In general, the activities of enzymes in brown adipose tissue (BAT) are more similar to those in white adipose tissue than those in liver. Thus the activities of the glycolytic enzymes hexokinase and 6-phosphofructokinase are high but those of glucose 6-phosphatase and fructose bisphosphatase are non-detectable in the two adipose tissues. The activity of HMG-CoA synthase was non-detectable in BAT indicating that this tissue, unlike liver, cannot produce ketone bodies from fatty acid oxidation but, since the tissue possesses a high activity of HMG-CoA lyase, it might produce ketone bodies from leucine catabolism. The findings suggest that 'metabolically' brown adipose tissue can be classified better as an adipose tissue than as a peripheral liver. A high activity of 3-oxoacid CoA transferase but a non-detectable activity of 3-hydroxybutyrate dehydrogenase suggests that BAT can utilise acetoacetate but not 3-hydroxybutyrate for heat generation during cold exposure plus starvation.
Publisher: Portland Press Ltd.
Date: 05-1997
DOI: 10.1042/BST025368S
Abstract: All academic institution contributes to the corpus of knowledge in some way. To keep expanding, the resulting information and data must be collected in a single area and shared throughout society. Knowledge developed in academic institutions is not adequately preserved or gathered, according to research. It has also been observed that the majority of the content or knowledge developed in academic institutes is unknown to the general public and is categorized as a literature review, which may be useful if proper coding is kept in the organization. The purposeful integration of humans, processes, and technology dedicated to developing, capturing, and executing an organization's creative infrastructure is known as a Knowledge Management (KM) method. Knowledge Management supports educational institutes in refining their capability to acquire and share information and knowledge, applying it to problem resolution and promoting research and continuous development. This paper advocates a holistic strategy for finding, analyzing, recording, retrieving, and distributing the whole of an administration's data properties. Databases, records, procedures, regulations and hitherto un-captured knowledge and talent in ordinary employees are s les of these properties. Higher education institutions can use KM as a tried and true approach to dealing with their problems. KM aids in the motivation of research as well as the promotion of partnerships and innovations in the future.
Publisher: Springer Netherlands
Date: 02-05-2015
Publisher: Elsevier BV
Date: 2004
DOI: 10.1016/J.BCP.2003.08.026
Abstract: The polymorphonuclear neutrophil (PMN)-respiratory burst plays a key role in host defense and inflammatory reactions. Modulation of this key neutrophil function by endogenous agents and the mechanisms involved are poorly understood. This study was designed to analyze the mechanisms involved in the effect of adrenaline on neutrophil superoxide anions production. Using the superoxide dismutase (SOD)-inhibitable cytochrome c reduction assay, we report here that the beta-adrenergic agonist, adrenaline at physiologic concentrations (5-100 nM) inhibited formyl-methionyl-leucyl-phenylalanine (fMLP)-stimulated but not phorbol-myristate-acetate (PMA)-stimulated PMN superoxide anion production. The inhibitory effect of adrenaline runs in parallel with an increase in intracellular levels of cAMP which was reversed by the protein kinase A (PKA) inhibitor H-89, suggesting a role for PKA in mediating the inhibitory effect of adrenaline on fMLP-induced superoxide production. Adrenaline at physiological concentrations did not inhibit the fMLP-stimulated membrane translocation of the NADPH oxidase components p47phox and p67phox, nor the fMLP-stimulated phosphorylation of p47phox. However, adrenaline strongly depressed the activity of the cytosolic isoform of Phospholipase A(2) (cPLA(2)). We suggest that adrenaline inhibits fMLP induced superoxide production upstream of the NADPH oxidase via a mechanism involving PKA and cPLA(2).
Publisher: Elsevier BV
Date: 02-2006
DOI: 10.1016/J.LFS.2005.07.038
Abstract: Commercially available lipid emulsions for parenteral nutrition are mainly composed by long chain triacylglycerol containing a high proportion of linoleic acid (LA) or oleic acid (OA). The immunological impact of such therapy is particularly important because parenteral diets are often administered to critically ill patients as a mechanism to supply adequate nutrition during catabolic stress conditions. The comparative toxicity of OA and LA on human lymphocytes and the type of cell death induced by these fatty acids were determined in vitro. Parameters of cell death were investigated by flow cytometry-cell viability, DNA fragmentation, phosphatidylserine externalization, mitochondrial depolarization, neutral lipid accumulation and production of reactive oxygen species-and by fluorescence microscopy-chromatin condensation. Additionally a spectrofluorometric assay was employed to determine the activities of caspase--3, 6 and 8. Evidence is presented herein that OA is less toxic to human lymphocytes than LA. However, both fatty acids promoted apoptosis and necrosis of these cells. The mechanism of cell death induced by OA involved activation of caspase 3 while the mechanism of death induced by LA involved mitochondrial depolarization and ROS production. Importantly, neutral lipid accumulation may be a mechanism to protect lymphocytes against the toxicity induced by OA. OA may offer an immunological less problematic alternative to LA with respect to fatty acid composition of parenteral nutritional emulsions.
Publisher: Elsevier BV
Date: 07-1997
DOI: 10.1016/S0899-9007(97)83034-1
Abstract: The activity of glutaminase is high in lymphoid organs, lymphocytes and macrophages and increases in the popliteal lymph node in response to an immunological challenge. Consistent with this high activity, glutamine is utilised at a high rate by resting lymphocytes and macrophages in culture. Mitogenic stimulation of lymphocytes increases both glutaminase activity and the rate of glutamine utilisation. The major products of glutamine utilisation by lymphocytes and macrophages in culture are glutamate, aspartate, lactate and ammonia < 25% of the glutamine used is completely oxidised. It is suggested that the high rate of glutamine utilisation by cells of the immune system serves to maintain a high intracellular concentration of intermediates of biosynthetic pathways such that optimal rates of DNA, RNA and protein synthesis can be maintained. In the absence of glutamine, lymphocytes do not proliferate in vitro proliferation increases greatly as the glutamine concentration increases. The synthesis of interleukin-2 by lymphocytes and of interleukin-1 by macrophages is glutamine-dependent. Macrophage-mediated phagocytosis is influenced by glutamine availability. Glutamine is synthesized in skeletal muscle. Skeletal muscle and plasma glutamine levels are lowered by sepsis, injury, burns, surgery and endurance exercise and in the overtrained athlete. These observations indicate that a significant depletion of the skeletal muscle glutamine pool is characteristic of trauma and it has been suggested that the lowered plasma glutamine concentration contributes, at least in part, to the immunosuppression which accompanies such situations. Beneficial effects of the provision of glutamine or its precursors have been reported in patients following surgery, radiation treatment or bone marrow transplantation or suffering from injury, sepsis or burns.
Publisher: Wiley
Date: 20-10-2006
DOI: 10.1111/J.1742-4658.2006.05513.X
Abstract: Prolonged exposure of pancreatic beta cells to the sulfonylureas glibencamide and tolbutamide induces subsequent desensitization to the actions of these drugs. The precise mechanisms underlying this desensitization remain unknown, prompting the present study, which investigated the impact of prolonged sulfonylurea exposure on glucose and energy metabolism using clonal pancreatic BRIN-BD11 beta cells. Following prolonged exposure to tolbutamide, BRIN-BD11 beta cells were incubated in the presence of [U-(13)C]glucose, and isotopomer analysis revealed that there was a change in the ratio of flux through pyruvate carboxylase (EC 6.4.1.1) and pyruvate dehydrogenase (EC 1.2.4.1, EC 2.3.1.12, EC 1.8.1.4). Energy status in intact BRIN-BD11 cells was determined using (31)P-NMR spectroscopy. Exposure to tolbutamide did not alter the nucleotide triphosphate levels. Collectively, data from the present study demonstrate that prolonged exposure of beta cells to tolbutamide results in changes in flux through key enzymes involved in glucose metabolism that, in turn, may impact on glucose-induced insulin secretion.
Publisher: Informa UK Limited
Date: 10-2015
DOI: 10.2147/DDDT.S92467
Publisher: MDPI AG
Date: 06-08-2021
DOI: 10.3390/IJMS22168460
Abstract: Macrophages and lymphocytes demonstrate metabolic plasticity, which is dependent partly on their state of activation and partly on the availability of various energy yielding and biosynthetic substrates (fatty acids, glucose, and amino acids). These substrates are essential to fuel-based metabolic reprogramming that supports optimal immune function, including the inflammatory response. In this review, we will focus on metabolism in macrophages and lymphocytes and discuss the role of fatty acids in governing the phenotype, activation, and functional status of these important cells. We summarize the current understanding of the pathways of fatty acid metabolism and related mechanisms of action and also explore possible new perspectives in this exciting area of research.
Publisher: MDPI AG
Date: 23-01-2021
DOI: 10.3390/JCM10030441
Abstract: Congenital Generalized Lipodystrophy type 2 (CGL2) is the most severe form of lipodystrophy and is caused by mutations in the BSCL2 gene. Affected patients exhibit a near complete lack of adipose tissue and suffer severe metabolic disease. A recent study identified infection as a major cause of death in CGL2 patients, leading us to examine whether Bscl2 loss could directly affect the innate immune response. We generated a novel mouse model selectively lacking Bscl2 in the myeloid lineage (LysM-B2KO) and also examined the function of bone-marrow-derived macrophages (BMDM) isolated from global Bscl2 knockout (SKO) mice. LysM-B2KO mice failed to develop lipodystrophy and metabolic disease, providing a model to study the direct role of Bscl2 in myeloid lineage cells. Lipopolysaccharide-mediated stimulation of inflammatory cytokines was not impaired in LysM-B2KO mice or in BMDM isolated from either LysM-B2KO or SKO mice. Additionally, intracellular fate and clearance of bacteria in SKO BMDM challenged with Staphylococcus aureus was indistinguishable from that in BMDM isolated from littermate controls. Overall, our findings reveal that selective Bscl2 deficiency in macrophages does not critically impact the innate immune response to infection. Instead, an increased susceptibility to infection in CGL2 patients is likely to result from severe metabolic disease.
Publisher: Portland Press Ltd.
Date: 10-1998
DOI: 10.1042/CS19980194
Publisher: Wiley
Date: 26-08-2013
Publisher: Portland Press Ltd.
Date: 02-2004
DOI: 10.1042/CS20030261
Abstract: Insulin-resistant states such as obesity can result in an increase in the function and mass of pancreatic β-cells, so that insulin secretion is up-regulated and Type II diabetes does not develop. However, expansion of β-cell mass is not indefinite and may well decrease with time. Changes in circulating concentrations of nutritional factors, such as fatty acids and/or glucose, may lead to a reduction in β-cell mass in vivo. Few previous studies have attempted to explore the interplay between glucose, amino acids and fatty acids with respect to β-cell mass and functional integrity. In the present study, we demonstrate that culture of clonal BRIN-BD11 cells for 24 h with the polyunsaturated fatty acid arachidonic acid (AA) increased β-cell proliferation and enhanced alanine-stimulated insulin secretion. These effects of AA were associated with significant decreases in the cellular consumption of D-glucose and L-alanine as well as decreased rates of production of nitric oxide and ammonia. Conversely 24 h exposure to the saturated fatty acid palmitic acid (PA) was found to decrease β-cell viability (by increasing apoptosis), increase the intracellular concentration of triacylglycerol (triglyceride), while inhibiting alanine-stimulated insulin secretion. These effects of PA were associated with significant increases in D-glucose and L-glutamine consumption as well as nitric oxide and ammonia production. However, L-alanine consumption was decreased in the presence of PA. The effects of AA, but not PA, were additionally dependent on glucose concentration. These studies indicate that AA may have a critical role in maintaining the appropriate mass and function of islet β-cells by influencing rates of cell proliferation and insulin secretion. This regulatory effect may be compromised by high circulating levels of glucose and/or PA, both of which are elevated in Type II diabetes and may impact upon dysfunctional and apoptotic intracellular events in the β-cell.
Publisher: Public Library of Science (PLoS)
Date: 25-02-2015
Publisher: Portland Press Ltd.
Date: 03-1988
DOI: 10.1042/BJ2500383
Abstract: 1. The activities of pyruvate dehydrogenase in rat lymphocytes and mouse macrophages are much lower than those of the key enzymes of glycolysis and glutaminolysis. However, the rates of utilization of pyruvate (at 2 mM), from the incubation medium, are not markedly lower than the rate of utilization of glucose by incubated lymphocytes or that of glutamine by incubated macrophages. This suggests that the low rate of oxidation of pyruvate produced from either glucose or glutamine in these cells is due to the high capacity of lactate dehydrogenase, which competes with pyruvate dehydrogenase for pyruvate. 2. Incubation of either macrophages or lymphocytes with dichloroacetate had no effect on the activity of subsequently isolated pyruvate dehydrogenase incubation of mitochondria isolated from lymphocytes with dichloroacetate had no effect on the rate of conversion of [1-14C]pyruvate into 14CO2, and the double-reciprocal plot of [1-14C]pyruvate concentration against rate of 14CO2 production was linear. In contrast, ADP or an uncoupling agent increased the rate of 14CO2 production from [1-14C]pyruvate by isolated lymphocyte mitochondria. These data suggest either that pyruvate dehydrogenase is primarily in the a form or that pyruvate dehydrogenase in these cells is not controlled by an interconversion cycle, but by end-product inhibition by NADH and/or acetyl-CoA. 3. The rate of conversion of [3-14C]pyruvate into CO2 was about 15% of that from [1-14C]pyruvate in isolated lymphocytes, but was only 1% in isolated lymphocyte mitochondria. The inhibitor of mitochondrial pyruvate transport, alpha-cyano-4-hydroxycinnamate, inhibited both [1-14C]- and [3-14C]-pyruvate conversion into 14CO2 to the same extent, and by more than 80%. 4. Incubations of rat lymphocytes with concanavalin A had no effect on the rate of conversion of [1-14C]pyruvate into 14CO2, but increased the rate of conversion of [3-14C]pyruvate into 14CO2 by about 50%. This suggests that this mitogen causes a stimulation of the activity of pyruvate carboxylase.
Publisher: Portland Press Ltd.
Date: 1999
DOI: 10.1042/CS0960089
Abstract: Macrophages and monocytes are cells with a large capacity for cytokine production. Cytokines produced by these cells are not preformed and released upon stimulation, but must be transcribed and translated. Although much is known concerning the regulation of the latter processes at the molecular level, the role of exogenous amino acids in the secretory process has not been actively investigated. Glutamine is utilized by macrophages at a much faster rate than any other amino acid. The role for high rates of glutamine utilization in macrophages or monocytes is not fully understood. We demonstrate here that the rates of lipopolysaccharide-stimulated tumour necrosis factor-α secretion from bacillus Calmette–Guérin (BCG)-activated murine peritoneal macrophages and lipopolysaccharide-stimulated interleukin-8 production from human monocytes are dependent upon extracellular glutamine concentration. We also demonstrate that potent inhibition of cytokine production can be achieved by incubating macrophages or monocytes in the presence of the glutaminase inhibitor 6-diazo-5-oxo-norleucine. On co-culture of BCG-activated macrophages and the clonal pancreatic β-cell line BRIN-BD11, macrophage-specific β-cell death was significantly reduced on prior exposure of macrophages to 6-diazo-5-oxo-norleucine. Thus glutamine metabolism may be essential for generation of cytotoxic products from macrophages, including tumour necrosis factor-α.
Publisher: Elsevier BV
Date: 02-2016
DOI: 10.1016/J.YEXCR.2016.02.008
Abstract: Malignant mesothelioma (MM) is an aggressive cancer, characterized by rapid progression, along with late metastasis and poor patient prognosis. It is resistant to many forms of standard anti-cancer treatment. In this study, we determined the effect of secreted frizzled-related protein 4 (sFRP4), a Wnt pathway inhibitor, on cancer cell proliferation and metabolism using the JU77 mesothelioma cell line. Treatment with sFRP4 (250 pg/ml) resulted in a significant reduction of cell proliferation. The addition of the Wnt activator Wnt3a (250 pg/ml) or sFRP4 had no significant effect on ATP production and glucose utilisation in JU77 cells at both the 24 and 48 h time points examined. We also examined their effect on Akt and Glycogen synthase kinase-3 beta (GSK3β) phosphorylation, which are both important components of Wnt signalling and glucose metabolism. We found that protein phosphorylation of Akt and GSK3β varied over the 24h and 48 h time points, with constitutive phosphorylation of Akt at serine 473 (pAkt) decreasing to its most significant level when treated with Wnt3a+sFRP4 at the 24h time point. A significant reduction in the level of Cytochrome c oxidase was observed at the 48 h time point, when sFRP4 and Wnt3a were added in combination. We conclude that sFRP4 may function, in part, to reduce/alter cancer cell metabolism, which may lead to sensitisation of cancer cells to chemotherapeutics, or even cell death.
Publisher: Elsevier BV
Date: 10-2013
Publisher: Portland Press Ltd.
Date: 03-02-2014
DOI: 10.1042/CS20130678
Abstract: eHSP72 (extracellular heat-shock protein 72) is increased in the plasma of both types of diabetes and is positively correlated with inflammatory markers. Since aging is associated with a low-grade inflammation and IR (insulin resistance), we aimed to: (i) analyse the concentration of eHSP72 in elderly people and determine correlation with insulin resistance, and (ii) determine the effects of eHSP72 on β-cell function and viability in human and rodent pancreatic β-cells. Fasting blood s les were collected from 50 older people [27 females and 23 males 63.4±4.4 years of age BMI (body mass index)=25.5±2.7 kg/m2]. Plasma s les were analysed for eHSP72, insulin, TNF (tumour necrosis factor)-α, leptin, adiponectin and cortisol, and glycaemic and lipid profile. In vitro studies were conducted using rodent islets and clonal rat and human pancreatic β-cell lines (BRIN-BD11 and 1.1B4 respectively). Cells/islets were incubated for 24 h with eHSP72 (0, 0.2, 4, 8 and 40 ng/ml). Cell viability was measured using three different methods. The impact of HSP72 on β-cell metabolic status was determined using Seahorse Bioscience XFe96 technology. To assess whether the effects of eHSP72 were mediated by Toll-like receptors (TLR2/TLR4), we co-incubated rodent islets with eHSP72 and the TLR2/TLR4 inhibitor OxPAPC (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine 30 μg/ml). We found a positive correlation between plasma eHSP72 and HOMA-IR (homoeostasis model assessment of IR) (r=0.528, P& .001), TNF-α (r=0.389, P& .014), cortisol (r=0.348, P& .03) and leptin/adiponectin (r=0.334, P& .03). In the in vitro studies, insulin secretion was decreased in an eHSP72 dose-dependent manner in BRIN-BD11 cells (from 257.7±33 to 84.1±10.2 μg/mg of protein per 24 h with 40 ng/ml eHSP72), and in islets in the presence of 40 ng/ml eHSP72 (from 0.48±0.07 to 0.33±0.009 μg/20 islets per 24 h). Similarly, eHSP72 reduced β-cell viability (at least 30% for BRIN-BD11 and 10% for 1.1B4 cells). Bioenergetic studies revealed that eHSP72 altered pancreatic β-cell metabolism. OxPAPC restored insulin secretion in islets incubated with 40 ng/ml eHSP72. In conclusion, we have demonstrated a positive correlation between eHSP72 and IR. In addition, we suggest that chronic eHSP72 exposure may mediate β-cell failure.
Publisher: Portland Press Ltd.
Date: 05-1994
DOI: 10.1042/BST022116S
Publisher: Springer Netherlands
Date: 22-12-2011
DOI: 10.1007/978-94-007-2869-1_10
Abstract: Mitochondria play a key role in energy metabolism and ATP production in many tissues, including skeletal muscle, cardiac muscle, brain and liver. Inherent disorders of mitochondria such as mDNA deletions cause major disruption of metabolism and can result in severe disease phenotypes. However, the incidence of such mDNA based disorders is extremely rare and cannot account for the dramatic rise in human metabolic diseases, which are characterised by defects in energy metabolism. Mitochondrial dysfunction characterized by reduced ATP generation and reduced mitochondrial number in skeletal muscle or reduced ATP generation and mitochondrial stimulus-secretion coupling in the pancreatic beta cell has been implicated in the pathology of chronic metabolic disease associated with type 2 diabetes mellitus and also with aging. Additionally the generation of ROS from mitochondria and other cellular sources may interfere in insulin signaling in muscle, contributing to insulin resistance. Reduced mitochondrial oxidative capacity coupled with increased ROS generation underlies the accumulation of intramuscular fat, insulin resistance and muscle dysfunction in aging. We will review the molecular basis for optimal mitochondrial function or mechanisms of dysfunction and correlate with pathology of identified diseases and aging.
Publisher: MDPI AG
Date: 11-12-2021
Abstract: Histone deacetylase (HDAC) inhibitors such as butyrate have been reported to reduce diabetes risk and protect insulin-secreting pancreatic β cells in animal models. However, studies on insulin-secreting cells in vitro have found that butyrate treatment resulted in impaired or inappropriate insulin secretion. Our study explores the effects of butyrate on insulin secretion by BRIN BD-11 rat pancreatic β cells and examined effects on the expression of genes implicated in β cell function. Robust HDAC inhibition with 5 mM butyrate or trichostatin A for 24 h in β cells decreased basal insulin secretion and content, as well as insulin secretion in response to acute stimulation. Treatment with butyrate also increased expression of the disallowed gene hexokinase I, possibly explaining the impairment to insulin secretion, and of TXNIP, which may increase oxidative stress and β cell apoptosis. In contrast to robust HDAC inhibition ( % after 24 h), low-dose and acute high-dose treatment with butyrate enhanced nutrient-stimulated insulin secretion. In conclusion, although protective effects of HDAC inhibition have been observed in vivo, potent HDAC inhibition impairs β cell function in vitro. The chronic low dose and acute high dose butyrate treatments may be more reflective of in vivo effects.
Publisher: Portland Press Ltd.
Date: 02-2003
DOI: 10.1042/CS20020223
Publisher: Portland Press Ltd.
Date: 19-09-2008
DOI: 10.1042/BST0360955
Abstract: Both stimulatory and detrimental effects of NEFAs (non-esterified fatty acids) on pancreatic β-cells have been recognized. Acute exposure of the pancreatic β-cell to high glucose concentrations and/or saturated NEFAs results in a substantial increase in insulin release, whereas chronic exposure results in desensitization and suppression of secretion followed by induction of apoptosis. Some unsaturated NEFAs also promote insulin release acutely, but they are less toxic to β-cells during chronic exposure and can even exert positive protective effects. In the present review, we focus on exogenous and endogenous effects of NEFAs, including the polyunsaturated fatty acid, arachidonic acid (or its metabolites generated from cyclo-oxygenase activity), on β-cell metabolism, and have explored the outcomes with respect to β-cell insulin secretion.
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/181643
Abstract: The prevalence of diabetes mellitus (DM) is increasing worldwide, a consequence of the alarming rise in obesity and metabolic syndrome (MetS). Oxidative stress and inflammation are key physiological and pathological events linking obesity, insulin resistance, and the progression of type 2 DM (T2DM). Unresolved inflammation alongside a “glucolipotoxic” environment of the pancreatic islets, in insulin resistant pathologies, enhances the infiltration of immune cells which through secretory activity cause dysfunction of insulin-secreting β -cells and ultimately cell death. Recent molecular investigations have revealed that mechanisms responsible for insulin resistance associated with T2DM are detected in conditions such as obesity and MetS, including impaired insulin receptor (IR) signalling in insulin responsive tissues, oxidative stress, and endoplasmic reticulum (ER) stress. The aim of the present review is to describe the evidence linking oxidative stress and inflammation with impairment of insulin secretion and action, which result in the progression of T2DM and other conditions associated with metabolic dysregulation.
Publisher: MDPI AG
Date: 13-12-2022
Abstract: Alzheimer’s disease (AD) and type 2 diabetes (T2D) are chronic diseases that share several pathological mechanisms, including insulin resistance and impaired insulin signalling. Their shared features have prompted the evaluation of the drugs used to manage diabetes for the treatment of AD. Insulin delivery itself has been utilized, with promising effects, in improving cognition and reducing AD related neuropathology. The most recent clinical trial involving intranasal insulin reported no slowing of cognitive decline however, several factors may have impacted the trial outcomes. Long-acting and rapid-acting insulin analogues have also been evaluated within the context of AD with a lack of consistent outcomes. This narrative review provided insight into how targeting insulin signalling in the brain has potential as a therapeutic target for AD and provided a detailed update on the efficacy of insulin, its analogues and the outcomes of human clinical trials. We also discussed the current evidence that warrants the further investigation of the use of the mimetics of insulin for AD. These small molecules may provide a modifiable alternative to insulin, aiding in developing drugs that selectively target insulin signalling in the brain with the aim to attenuate cognitive dysfunction and AD pathologies.
Publisher: Elsevier BV
Date: 11-2012
DOI: 10.1016/J.METABOL.2012.05.003
Abstract: Nitric oxide (NO·) exerts key regulatory functions including vasodilation and glucose uptake. Thus reduced NO· levels are associated with insulin resistance and hypertension. In this preliminary work we aimed to measure the levels of NO· metabolites in serum and skeletal muscle of obese and non-obese subjects, with or without type 2 diabetes mellitus (T2DM). Fifteen sedentary male participants [7 obese controls (C) vs 5 obese and 3 non-obese T2DM age 54±9 years] were selected according to their BMI (>30 kg/m(2) for obese and 23-27 kg/m(2) for non-obese participants) and evaluated for fasted values of blood glucose, HbA1c, lipid profile, serum CRP (C-reactive protein), erythrocyte glutathione (GSH) metabolism, plasma adiponectin, leptin and cytokines (TNF-α and INFγ), serum and skeletal muscle nitric oxide metabolites (nitrite and nitrates tNOx) and skeletal muscle nNOS and iNOS expression. Body composition was measured by whole body DEXA and muscle microbiopsy was performed in the vastus lateralis. We found that serum tNOx (total nitrite/nitrate μmol/L) was lower in obese T2DM group (12.7±3.5) when compared with their controls (21.1±2.4), although the non-obese group presented higher concentration of tNOx (33.8±7.2). Skeletal muscle nNOS was higher in obese controls, lower in non-obese T2DM and undetected in obese T2DM. On the other hand, expression of iNOS had an inverse relationship with nNOS, showing higher expression in obese T2DM, decrease in non-obese T2DM and absence in obese control group. tNOx levels (μmol/mg protein) were decreased in the non-obese T2DM group (12.07±0.59) when compared with the obese control (21.68±6.2) and the obese T2DM group (26.3±7.26). We conclude that the decreased serum NO∙ production in obese T2DM patients seems to be associated with adipose mass as lower adiposity was associated with normal NO∙ which was reduced in the skeletal muscle of the non-obese T2DM patients. We suggest that the lower adiposity (and higher adiponectin) in non-obese T2DM could be responsible for differential levels of NO∙ production and insulin resistance.
Publisher: Elsevier BV
Date: 11-2015
DOI: 10.1016/J.BIOCEL.2015.09.008
Abstract: Mesenchymal stem cells (MSCs) are multipotent precursor cells originating from several adult connective tissues. MSCs possess the ability to self-renew and differentiate into several lineages, and are recognized by the expression of unique cell surface markers. Several lines of evidence suggest that various signal transduction pathways and their interplay regulate MSC differentiation. To that end, a critical player in regulating MSC differentiation is a group of proteins encoded by the Wnt gene family, which was previously known for influencing various stages of embryonic development and cell fate determination. As MSCs have gained significant clinical attention for their potential applications in regenerative medicine, it is imperative to unravel the mechanisms by which molecular regulators control differentiation of MSCs for designing cell-based therapeutics. It is rather coincidental that the functional outcome(s) of Wnt-induced signals share similarities with cellular redox-mediated networks from the standpoint of MSC biology. Furthermore, there is evidence for a crosstalk between Wnt and redox signalling, which begs the question whether Wnt-mediated differentiation signals involve the intermediary role of reactive oxygen species. In this review, we summarize the impact of Wnt signalling on multi-lineage differentiation of MSCs, and attempt to unravel the intricate interplay between Wnt and redox signals.
Publisher: Public Library of Science (PLoS)
Date: 08-04-2013
Publisher: Springer Netherlands
Date: 2014
Publisher: Elsevier
Date: 2014
Publisher: Portland Press Ltd.
Date: 24-10-2005
DOI: 10.1042/CS20050149
Abstract: Acute effects of nutrient stimuli on pancreatic β-cell function are widely reported however, the chronic effects of insulinotropic amino acids, such as L-alanine, on pancreatic β-cell function and integrity are unknown. In the present study, the effects of prolonged exposure (24 h) to the amino acid L-alanine on insulin secretory function, gene expression and pro-inflammatory cytokine-induced apoptosis were studied using clonal BRIN-BD11 cells. Expression profiling of BRIN-BD11 cells chronically exposed to L-alanine was performed using oligonucleotide microarray analysis. The effect of alanine, the iNOS (inducible nitric oxide synthase) inhibitor NMA (NG-methyl-L-arginine acetate) or the iNOS and NADPH oxidase inhibitor DPI (diphenylene iodonium) on apoptosis induced by a pro-inflammatory cytokine mix [IL-1β (interleukin-1β), TNF-α (tumour necrosis factor-α) and IFN-γ (interferon-γ)] was additionally assessed by flow cytometry. Culture for 24 h with 10 mM L-alanine resulted in desensitization to the subsequent acute insulin stimulatory effects of L-alanine. This was accompanied by substantial changes in gene expression of BRIN-BD11 cells. Sixty-six genes were up-regulated & .8-fold, including many involved in cellular signalling, metabolism, gene regulation, protein synthesis, apoptosis and the cellular stress response. Subsequent functional experiments confirmed that L-alanine provided protection of BRIN-BD11 cells from pro-inflammatory cytokine-induced apoptosis. Protection from apoptosis was mimicked by NMA or DPI suggesting L-alanine enhances intracellular antioxidant generation. These observations indicate important long-term effects of L-alanine in regulating gene expression, secretory function and the integrity of insulin-secreting cells. Specific amino acids may therefore play a key role in β-cell function in vivo.
Publisher: Hindawi Limited
Date: 2015
DOI: 10.1155/2015/249205
Abstract: Recent evidence shows ergence between the concentrations of extracellular 70 kDa heat shock protein [eHSP70] and its intracellular concentrations [iHSP70] in people with type 2 diabetes (T2DM). A vital aspect regarding HSP70 physiology is its versatility to induce antagonistic actions, depending on the location of the protein. For ex le, iHSP70 exerts a powerful anti-inflammatory effect, while eHSP70 activates proinflammatory pathways. Increased eHSP70 is associated with inflammatory and oxidative stress conditions, whereas decreased iHSP70 levels are related to insulin resistance in skeletal muscle. Serum eHSP70 concentrations are positively correlated with markers of inflammation, such as C-reactive protein, monocyte count, and TNF- α , while strategies to enhance iHSP70 (e.g., heat treatment, chemical HSP70 inducers or coinducers, and physical exercise) are capable of reducing the inflammatory profile and the insulin resistance state. Here, we present recent findings suggesting that imbalances in the HSP70 status, described by the [eHSP70]/[iHSP70] ratio, may be determinant to trigger a chronic proinflammatory state that leads to insulin resistance and T2DM development. This led us to hypothesize that changes in this ratio value could be used as a biomarker for the management of the inflammatory response in insulin resistance and diabetes.
Publisher: Portland Press Ltd.
Date: 05-1997
DOI: 10.1042/BST025366S
Publisher: Elsevier BV
Date: 12-2006
DOI: 10.1016/J.CLNU.2006.03.004
Abstract: The effect of a docosahexaenoic acid (DHA)-rich fish oil (FO) supplementation on human leukocyte function was investigated. Ten male volunteers were supplemented with 3g/day FO containing 26% eicosapentaenoic acid (EPA, 20:5, n-3) and 54% DHA (22:6, n-3) for 2 months. FO supplementation changed the fatty acid (FA) composition of leukocytes resulting in an increase of n-3/n-6 ratio from 0.18 to 0.62 in lymphocytes and from 0.15 to 0.70 in neutrophils. DHA-rich FO stimulated an increase in phagocytic activity by 62% and 145% in neutrophils and monocytes, respectively. Neutrophil chemotactic response was increased by 128%. The rate of production of reactive oxygen species by neutrophils was also increased, as it was with lymphocyte proliferation. These changes were partially reversed after a 2-month wash out period. With respect to cytokine production by lymphocytes, interleukin (IL)-4 release was not altered, whereas secretions of IL-10, interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha were raised. These results are in contrast to those described by others using EPA-rich FO supplementation. Lymphocyte pleiotropic gene expression was analyzed by a macroarray technique. Of the analyzed genes (588 in total), 77 were modified by the supplementation. FO supplementation resulted in up-regulation of 6 genes (GATA binding protein 2, IL-6 signal transducer, transforming growth factor alpha, TNF, heat shock 90kDa protein 1-alpha and heat shock protein 70kDa 1A) and a down regulation of 71 genes (92.2% of total genes changed). The largest functional group of altered genes was that related to signaling pathways (22% of the total modified genes). Therefore, although EPA and DHA are members of n-3 FA family, changes in the proportion of DHA and EPA exert different effects on neutrophil, monocyte and lymphocyte function, which may be a result of specific changes in gene expression.
Publisher: Portland Press Ltd.
Date: 09-2009
DOI: 10.1042/CS20090126
Abstract: In the present study, we have investigated the effects of the transduction with recombinant adenovirus AdCA-Aralar1 (aspartate–glutamate carrier 1) on the metabolism, function and secretory properties of the glucose- and amino-acid-responsive clonal insulin-secreting cell line BRIN-BD11. Aralar1 overexpression increased long-term (24 h) and acute (20 min) glucose- and amino-acid-stimulated insulin secretion, cellular glucose metabolism, L-alanine and L-glutamine consumption, cellular ATP and glutamate concentrations, and stimulated glutamate release. However, cellular triacylglycerol and glycogen contents were decreased as was lactate production. These findings indicate that increased malate–aspartate shuttle activity positively shifted β-cell metabolism, thereby increasing glycolysis capacity, stimulus–secretion coupling and, ultimately, enhancing insulin secretion. We conclude that Aralar1 is a key metabolic control site in insulin-secreting cells.
Publisher: Research Square Platform LLC
Date: 17-01-2023
DOI: 10.21203/RS.3.RS-2319322/V1
Abstract: Background : Leucine (Leu) supplementation per se could benefit fat-free mass (FFM)/function and improve glucose metabolism. Objectives: To determine whether leucine supplementation during caloric restriction blunted the loss of FFM, increased the loss of fat mass (FM) and impacted glucose tolerance. Design : Thirty-seven adults, aged 20-65 y with increased waist circumference ( cm for females and cm for males) and at least another component of metabolic syndrome (MetS) were studied in a parallel, double blind randomized control trial (RCT). Participants were allocated randomly to either an intervention (leucine – 3 g/d) or placebo (lactose - 2.67 g/d) group, while following an in idualised calorie-restricted diet over an 8-week period. Body composition (DEXA), oral glucose tolerance test (OGTT), insulin and components of MetS were measured before and after the trial. Analysis of covariance assessed the effect of the leucine intervention on an intention-to-treat (ITT) principle. Bootstrapping method with 1000 bootstrap s les was used to derive parameter estimates, standard errors, p values, and 95% confidence intervals for all outcomes. Results: Adjusted for baseline values and other covariates, FFM (p=0.045) and lean tissue mass (LTM) (p=0.050) were significantly higher following Leu. These outcomes were modified by a significant treatment x gender interaction that indicated Leu had the greater effect in men. Adjusted for body composition changes, there were no differences in insulin sensitivity, oral glucose tolerance, or MetS components. Conclusio n: Short-term leucine supplementation resulted in a greater preservation of FFM and LTM particularly in men.
Publisher: Elsevier BV
Date: 07-1986
DOI: 10.1016/0006-291X(86)90282-2
Abstract: In lymphocytes of the rat, pyruvate kinase, phosphoenolpyruvate carboxykinase and NADP+-linked malate dehydrogenase (decarboxylating) are distributed almost exclusively in the cytosol whereas pyruvate carboxylase is distributed almost entirely in the mitochondria. For NAD+-linked malate dehydrogenase and aspartate aminotransferase approximately 80% and 40%, respectively, are in the cytosolic compartment. Since glutaminase is present in the mitochondria, glutamine is converted to malate within the mitochondria but further metabolism of the malate is likely to occur in the cytosol. Hence pyruvate produced from this malate, via oxaloacetate and phosphoenolpyruvate carboxykinase, may be rapidly converted to lactate, so restricting the entry of pyruvate into the mitochondria and explaining why very little glutamine is completely oxidised in these cells despite a high capacity of the Krebs cycle.
Publisher: Wiley
Date: 23-12-2008
DOI: 10.1002/CBF.1533
Abstract: Short chain fatty acids (SCFAs) are metabolic by products of anaerobic bacteria fermentation. These fatty acids, despite being an important fuel for colonocytes, are also modulators of leukocyte function. The aim of this study was to evaluate the effects of SCFAs (acetate, propionate, and butyrate) on function of neutrophils, and the possible mechanisms involved. Neutrophils obtained from rats by intraperitoneal lavage 4 h after injection of oyster glycogen solution (1%) were treated with non toxic concentrations of the fatty acids. After that, the following measurements were performed: phagocytosis and destruction of Candida albicans, production of ROS (O(2)(*-), H(2)O(2), and HOCl) and degranulation. Gene expression (p47(phox) and p22(phox)) and protein phosphorylation (p47(phox)) were analyzed by real time reverse transcriptase chain reaction (RT-PCR) and Western blotting, respectively. Butyrate inhibited phagocytosis and killing of C. albicans. This SCFA also had an inhibitory effect on production of O(2)(*-), H(2)O(2), and HOCl by neutrophils stimulated with PMA or fMLP. This effect of butyrate was not caused by modulation of expression of NADPH oxidase subunits (p47(phox) and p22(phox)) but it was in part due to reduced levels of p47(phox) phosphorylation and an increase in the concentration of cyclic AMP. Acetate increased the production of O(2)(*-) and H(2)O(2) in the absence of stimuli but had no effect on phagocytosis and killing of C. albicans. Propionate had no effect on the parameters studied. These results suggest that butyrate can modulate neutrophil function and thus could be important in inflammatory neutrophil-associated diseases.
Publisher: Portland Press Ltd.
Date: 10-1998
DOI: 10.1042/CS0950397
Abstract: 1.The intermediates of biochemical cycles are commonly utilized for biosynthetic processes thus at least one intermediate must be replenished de novo to provide constant flux through the cycle. The utilization of l-arginine for NO synthesis in macrophages may thus reduce the concentration of intermediates of the urea cycle. It is possible that a glutamine-utilizing pathway exists in mononuclear phagocytes that may connect with the urea cycle. 2.In this paper we report that mouse peritoneal resident and Bacillus Calmette–Guerin (BCG)-activated macrophages and human monocytes are capable of utilizing glutamine at high rates, contain sufficient activity of the enzymes required to convert glutamine to citrulline (and subsequently citrulline to arginine) to account for observed rates of nitrite synthesis in the absence of extracellular l-arginine, and will release nitrite when exposed to intermediates of the proposed glutamine → arginine pathway. 3.The rate of nitrite production (in the absence of extracellular arginine) was reduced by culturing macrophages or monocytes in the presence of the glutaminase inhibitor 6-diazo 5-oxo norleucine. 4.The rate and extent of arginase secretion, glutamine utilization, nitrite production (basal and lipopolysaccharide-stimulated) and phosphate-dependent glutaminase activity from BCG-activated macrophages was increased compared with resident cells. 5.We suggest that the elevated arginase secretion rates in activated macrophages would effectively increase the intracellular concentration of arginine available for conversion to NO via inducible nitric oxide synthase, the expression of which is known to increase on activation of macrophages or monocytes. Additionally, the rate of l-arginine biosynthesis from glutamine may be increased on immunostimulation of the macrophage.
Publisher: Elsevier BV
Date: 05-2016
DOI: 10.1016/J.MCE.2016.02.004
Abstract: Pigment epithelium-derived factor (PEDF) is a multifunctional glycoprotein, associated with lipid catabolism and insulin resistance. In the present study, PEDF increased chronic and acute insulin secretion in a clonal rat β-cell line BRIN-BD11, without alteration of glucose consumption. PEDF also stimulated insulin secretion from primary mouse islets. Seahorse flux analysis demonstrated that PEDF did not change mitochondrial respiration and glycolytic function. The cytosolic presence of the putative PEDF receptor - adipose triglyceride lipase (ATGL) - was identified, and ATGL associated stimulation of glycerol release was robustly enhanced by PEDF, while intracellular ATP levels increased. Addition of palmitate or ex vivo stimulation with inflammatory mediators induced β-cell dysfunction, effects not altered by the addition of PEDF. In conclusion, PEDF increased insulin secretion in BRIN-BD11 and islet cells, but had no impact on glucose metabolism. Thus elevated lipolysis and enhanced fatty acid availability may impact insulin secretion following PEDF receptor (ATGL) stimulation.
Publisher: Portland Press Ltd.
Date: 12-2007
DOI: 10.1042/CS20060115
Abstract: Both stimulatory and detrimental effects of NEFAs (non-esterified fatty acids) on pancreatic β-cells have been recognized. Acute exposure of the pancreatic β-cell to high glucose concentrations and/or saturated NEFAs results in a substantial increase in insulin release, whereas chronic exposure results in desensitization and suppression of secretion, followed by induction of apoptosis. Some unsaturated NEFAs also promote insulin release acutely, but they are less toxic to β-cells during chronic exposure and can even exert positive protective effects. Therefore changes in the levels of NEFAs are likely to be important for the regulation of β-cell function and viability under physiological conditions. In addition, the switching between endogenous fatty acid synthesis or oxidation in the β-cell, together with alterations in neutral lipid accumulation, may have critical implications for β-cell function and integrity. Long-chain acyl-CoA (formed from either endogenously synthesized or exogenous fatty acids) controls several aspects of β-cell function, including activation of specific isoenzymes of PKC (protein kinase C), modulation of ion channels, protein acylation, ceramide formation and/or NO-mediated apoptosis, and transcription factor activity. In this review, we describe the effects of exogenous and endogenous fatty acids on β-cell metabolism and gene and protein expression, and have explored the outcomes with respect to insulin secretion and β-cell integrity.
Publisher: Wiley
Date: 07-06-2013
Abstract: The behavior of proteins and polypeptides at electrified aqueous-organic interfaces is of benefit in label-free detection strategies. In this work, rat amylin (or islet amyloid polypeptide) was studied at the interface formed between aqueous liquid and gelled organic phases. Amylin is a polypeptide that is co-secreted with insulin from islet beta-cells and is implicated in fibril formation. In this study, rat amylin was used, which does not undergo aggregation. The polypeptide underwent an interfacial transfer process, from water to the gelled organic phase, under applied potential stimulation. Cyclic voltammetry revealed steady-state forward and peak-shaped reverse voltammograms, which were consistent with diffusion-controlled water-to-organic transfer and thin-film stripping or desorptive back-transfer. The diffusion-controlled forward current was greater when amylin was present in an acidic aqueous phase than when it was present in an aqueous phase at physiological pH this reflects the greater charge on the polypeptide under acidic conditions. The amylin transfer current was concentration dependent over the range 2-10 μM, at both acidic and physiological pH. At physiological pH, amylin was selectively detected in the presence of a protein mixture, which illustrated the bioanalytical possibilities for this electrochemical behavior.
Publisher: Springer Science and Business Media LLC
Date: 23-06-2021
DOI: 10.1038/S41387-021-00162-3
Abstract: Various nutrients can change cell structure, cellular metabolism, and cell function which is particularly important for cells of the immune system as nutrient availability is associated with the activation and function of erse immune subsets. The most important nutrients for immune cell function and fate appear to be glucose, amino acids, fatty acids, and vitamin D. This perspective will describe recently published information describing the mechanism of action of prominent nutritional intervention agents where evidence exists as to their action and potency.
Publisher: MDPI AG
Date: 04-01-2022
Abstract: Irreversible pancreatic β-cell damage may be a result of chronic exposure to supraphysiological glucose or lipid concentrations or chronic exposure to therapeutic anti-diabetic drugs. The β-cells are able to respond to blood glucose in a narrow concentration range and release insulin in response, following activation of metabolic pathways such as glycolysis and the TCA cycle. The β-cell cannot protect itself from glucose toxicity by blocking glucose uptake, but indeed relies on alternative metabolic protection mechanisms to avoid dysfunction and death. Alteration of normal metabolic pathway function occurs as a counter regulatory response to high nutrient, inflammatory factor, hormone or therapeutic drug concentrations. Metabolic reprogramming is a term widely used to describe a change in regulation of various metabolic enzymes and transporters, usually associated with cell growth and proliferation and may involve reshaping epigenetic responses, in particular the acetylation and methylation of histone proteins and DNA. Other metabolic modifications such as Malonylation, Succinylation, Hydroxybutyrylation, ADP-ribosylation, and Lactylation, may impact regulatory processes, many of which need to be investigated in detail to contribute to current advances in metabolism. By describing multiple mechanisms of metabolic adaption that are available to the β-cell across its lifespan, we hope to identify sites for metabolic reprogramming mechanisms, most of which are incompletely described or understood. Many of these mechanisms are related to prominent antioxidant responses. Here, we have attempted to describe the key β-cell metabolic adaptions and changes which are required for survival and function in various physiological, pathological and pharmacological conditions.
Publisher: Wiley
Date: 30-07-2013
DOI: 10.1113/EXPPHYSIOL.2013.073809
Abstract: Using the cystine dimethylester (CDME) loading technique to achieve elevated lysosomal cystine levels, ATP depletion has previously been postulated to be responsible for the renal dysfunction in cystinosis, a genetic disorder characterized by an excessive accumulation of cystine in the lysosomes. However, this is unlikely to be the sole factor responsible for the complexity of cell stress associated with cystinosis. Moreover, CDME has been shown to induce a direct toxic effect on mitochondrial ATP generation. Using a human-derived proximal tubular epithelial cell line, we compared the effects of CDME loading with small interfering RNA-mediated cystinosin, lysosomal cystine transporter (CTNS) gene silencing on glutathione redox status, reactive oxygen species levels, oxidative stress index, antioxidant enzyme activities and ATP generating capacity. The CDME-loaded cells displayed increased total glutathione content, extensive superoxide depletion, augmented oxidative stress index, decreased catalase activity, normal superoxide dismutase activity and compromised ATP generation. In contrast, cells subjected to CTNS gene inhibition demonstrated decreased total glutathione content, increased superoxide levels, unaltered oxidative stress index, unaltered catalase activity, induction of superoxide dismutase activity and normal ATP generation. Our data indicate that many CDME-induced effects are independent of lysosomal cystine accumulation, which further underscores the limited value of CDME loading for studying the pathogenesis of cystinosis. CTNS gene inhibition, which results in intracellular cystine accumulation, is a more realistic approach for investigating biochemical alterations in cystinosis.
Publisher: Portland Press Ltd.
Date: 05-1997
DOI: 10.1042/BST025367S
Publisher: MDPI AG
Date: 02-11-2020
DOI: 10.3390/IJMS21218204
Abstract: Type 2 diabetes (T2D) and Alzheimer’s disease (AD) are growing in prevalence worldwide. The development of T2D increases the risk of AD disease, while AD patients can show glucose imbalance due to an increased insulin resistance. T2D and AD share similar pathological features and underlying mechanisms, including the deposition of amyloidogenic peptides in pancreatic islets (i.e., islet amyloid polypeptide IAPP) and brain (β-Amyloid Aβ). Both IAPP and Aβ can undergo misfolding and aggregation and accumulate in the extracellular space of their respective tissues of origin. As a main response to protein misfolding, there is evidence of the role of heat shock proteins (HSPs) in moderating T2D and AD. HSPs play a pivotal role in cell homeostasis by providing cytoprotection during acute and chronic metabolic stresses. In T2D and AD, intracellular HSP (iHSP) levels are reduced, potentially due to the ability of the cell to export HSPs to the extracellular space (eHSP). The increase in eHSPs can contribute to oxidative damage and is associated with various pro-inflammatory pathways in T2D and AD. Here, we review the role of HSP in moderating T2D and AD, as well as propose that these chaperone proteins are an important link in the relationship between T2D and AD.
Publisher: IMR Press
Date: 2011
DOI: 10.2741/3690
Abstract: Aberrant alterations in glucose and lipid concentrations and their pathways of metabolism are a hallmark of diabetes. However, much less is known about alterations in concentrations of amino acids and their pathways of metabolism in diabetes. In this review we have attempted to highlight, integrate and discuss common alterations in amino acid metabolism in a wide variety of cells and tissues and relate these changes to alterations in endocrine, physiologic and immune function in diabetes.
Publisher: Wiley
Date: 2003
DOI: 10.1002/CBF.1003
Abstract: Glucose is widely accepted as the primary nutrient for maintenance and promotion of cell function. However, we propose that the 5-carbon amino acids, glutamine and glutamate, should be considered to be equally important for maintenance and promotion of cell function. The functions of glutamine are many and include: substrate for protein synthesis, anabolic precursor for muscle growth, acid-base balance in the kidney, substrate for ureogenesis in the liver, substrate for hepatic and renal gluconeogenesis, an oxidative fuel for intestine and cells of the immune system, inter-organ nitrogen transport, precursor for neurotransmitter synthesis, precursor for nucleotide and nucleic acid synthesis and precursor for glutathione production. Many of these functions are connected to the formation of glutamate from glutamine. We propose that the unique properties regarding concentration and routes of metabolism of these amino acids allow them to be used for a erse array of processes related to the specialized function of each of the glutamine utilizing cells. In this review we highlight the specialized aspects of glutamine/glutamate metabolism of different glutamine-utilizing cells and in each case relate key aspects of metabolism to cell function.
Publisher: Informa UK Limited
Date: 15-08-2014
Publisher: Springer Science and Business Media LLC
Date: 14-11-2013
DOI: 10.1007/S00421-013-2769-6
Abstract: To investigate the effect of 16 weeks of aerobic training performed at two different intensities on nitric oxide (tNOx) availability and iNOS/nNOS expression, oxidative stress (OS) and inflammation in obese humans with or without type 2 diabetes mellitus (T2DM). Twenty-five sedentary, obese (BMI > 30 kg/m2) males (52.8 ± 7.2 years) 12 controls versus 13 T2DM were randomly allocated to four groups that exercised for 30 min, three times per week either at low (Fat-Max 30-40% VO(2max)) or moderate (T(vent) 55-65 % VO(2max)) intensity. Before and after training, blood and muscle s les (v. lateralis) were collected. Baseline erythrocyte glutathione was lower (21.8 ± 2.8 vs. 32.7 ± 4.4 nmol/ml) and plasma protein oxidative damage and IL-6 were higher in T2DM (141.7 ± 52.1 vs. 75.5 ± 41.6 nmol/ml). Plasma catalase increased in T2DM after T(vent) training (from 0.98 ± 0.22 to 1.96 ± 0.3 nmol/min/ml). T2DM groups demonstrated evidence of oxidative damage in response to training (elevated protein carbonyls). Baseline serum tNOx were higher in controls than T2DM (18.68 ± 2.78 vs. 12.34 ± 3.56 μmol/l). Training at T(vent) increased muscle nNOS and tNOx in the control group only. Pre-training muscle nNOS was higher in controls than in T2DMs, while the opposite was found for iNOS. No differences were found after training for plasma inflammatory markers. Exercise training did not change body composition or aerobic fitness, but improved OS markers, especially when performed at T(vent). Non-diabetics responded to T(vent) training by increasing muscle nNOS expression and tNOx levels in skeletal muscle while these parameters did not change in T2DM, perhaps due to higher insulin resistance (unchanged after intervention).
Publisher: Elsevier BV
Date: 09-2014
Publisher: Portland Press Ltd.
Date: 11-1996
DOI: 10.1042/BST024537S
Publisher: Portland Press Ltd.
Date: 17-01-2003
DOI: 10.1042/CS1040171
Abstract: We report here that monounsaturated fatty acids and polyunsaturated fatty acids (PUFAs) provoke the accumulation of neutral lipids and apoptosis in retinoic acid-treated HL-60 cells in a concentration- and time-dependent manner. The PUFAs (arachidonic acid, docosahexanoic acid and eicosapentaenoic acid) provoked higher levels of HL-60 apoptosis compared with the monounsaturated oleic acid or the saturated palmitic acid. Cell size and granularity were also altered by fatty acid treatment. The PUFA-induced apoptosis was correlated with increased activity of caspase 3 and caspase 9. Lipid peroxidation was also increased in the presence of PUFAs, but was not responsible for activating cell apoptosis. Lipid derived metabolites may be responsible for activation of caspases and induction of cell apoptosis.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for Philip Newsholme.