ORCID Profile
0000-0001-8361-2712
Current Organisations
Xi'an University of Architecture and Technology
,
University of Tasmania
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Publisher: Springer US
Date: 2023
Publisher: American Physiological Society
Date: 15-05-2015
DOI: 10.1152/AJPREGU.00412.2014
Abstract: Nitric oxide (NO) has been shown to be involved in skeletal muscle glucose uptake during contraction/exercise, especially in in iduals with Type 2 diabetes (T2D). To examine the potential mechanisms, we examined the effect of local NO synthase (NOS) inhibition on muscle glucose uptake and muscle capillary blood flow during contraction in healthy and T2D rats. T2D was induced in Sprague-Dawley rats using a combined high-fat diet (23% fat wt/wt for 4 wk) and low-dose streptozotocin injections (35 mg/kg). Anesthetized animals had one hindlimb stimulated to contract in situ for 30 min (2 Hz, 0.1 ms, 35 V) with the contralateral hindlimb rested. After 10 min, the NOS inhibitor, N G -nitro-l-arginine methyl ester (l-NAME 5 μM) or saline was continuously infused into the femoral artery of the contracting hindlimb until the end of contraction. Surprisingly, there was no increase in skeletal muscle NOS activity during contraction in either group. Local NOS inhibition had no effect on systemic blood pressure or muscle contraction force, but it did cause a significant attenuation of the increase in femoral artery blood flow in control and T2D rats. However, NOS inhibition did not attenuate the increase in muscle capillary recruitment during contraction in these rats. Muscle glucose uptake during contraction was significantly higher in T2D rats compared with controls but, unlike our previous findings in hooded Wistar rats, NOS inhibition had no effect on glucose uptake during contraction. In conclusion, NOS inhibition did not affect muscle glucose uptake during contraction in control or T2D Sprague-Dawley rats, and this may have been because there was no increase in NOS activity during contraction.
Publisher: Elsevier BV
Date: 04-2008
DOI: 10.1016/J.MVR.2007.11.002
Abstract: Contrast-enhanced ultrasound (CEU) has been used to measure muscle microvascular perfusion in vivo in response to exercise and insulin. In the present study we address whether CEU measurement of capillary volume is influenced by bulk flow and if measured capillary filling rate allows discrimination of different flow pattern changes within muscle. Three in vitro models were used: (i) bulk flow rate was varied within a single length of capillary tubing (ii) at constant bulk flow, capillary volume was increased 3-fold by joining lengths of capillary in series, and compared to a single length and (iii) at constant bulk flow, capillary volume was increased by sharing flow between a number of lengths of identical capillaries in parallel. The contrast medium for CEU was gas-filled albumin microbubbles. Pulsing interval (time) versus acoustic-intensity curves were constructed and from these, capillary volume and capillary filling rate were calculated. CEU estimates of capillary volume were not affected by changes in bulk flow. Furthermore, as CEU estimates of capillary volume increased, measures of capillary filling rate decreased, regardless of whether capillaries were connected in series or parallel. Therefore, CEU can detect a change in filling rate of the microvascular volume under measurement, but it can not be used to discriminate between different flow patterns within muscle that might account for capillary recruitment in vivo.
Publisher: American Physiological Society
Date: 05-2010
DOI: 10.1152/JAPPLPHYSIOL.01335.2009
Abstract: There is evidence that reactive oxygen species (ROS) contribute to the regulation of skeletal muscle glucose uptake during highly fatiguing ex vivo contraction conditions via AMP-activated protein kinase (AMPK). In this study we investigated the role of ROS in the regulation of glucose uptake and AMPK signaling during low-moderate intensity in situ hindlimb muscle contractions in rats, which is a more physiological protocol and preparation. Male hooded Wistar rats were anesthetized, and then N-acetylcysteine (NAC) was infused into the epigastric artery (125 mg·kg −1 ·h −1 ) of one hindlimb (contracted leg) for 15 min before this leg was electrically stimulated (0.1-ms impulse at 2 Hz and 35 V) to contract at a low-moderate intensity for 15 min. The contralateral leg did not receive stimulation or local NAC infusion (rest leg). NAC infusion increased ( P 0.05) plasma cysteine and cystine (by ∼360- and 1.4-fold, respectively) and muscle cysteine (by 1.5-fold, P = 0.001). Although contraction did not significantly alter muscle tyrosine nitration, reduced (GSH) or oxidized glutathione (GSSG) content, S-glutathionylation of protein bands at ∼250 and 150 kDa was increased ( P 0.05) ∼1.7-fold by contraction, and this increase was prevented by NAC. Contraction increased ( P 0.05) skeletal muscle glucose uptake 20-fold, AMPK phosphorylation 6-fold, ACCβ phosphorylation 10-fold, and p38 MAPK phosphorylation 60-fold, and the muscle fatigued by ∼30% during contraction and NAC infusion had no significant effect on any of these responses. This was despite NAC preventing increases in S-glutathionylation with contraction. In conclusion, unlike during highly fatiguing ex vivo contractions, local NAC infusion during in situ low-moderate intensity hindlimb contractions in rats, a more physiological preparation, does not attenuate increases in skeletal muscle glucose uptake or AMPK signaling.
Publisher: Wiley
Date: 14-11-2007
Publisher: National Library of Serbia
Date: 2020
Abstract: The physicochemical properties of slag are of great importance in pyrometallurgy. If there is a volatile component in the slag, evaporation will inevitably occur. As a result, the slag composition will change, and the measured results will be inconsistent with the original slag composition. Therefore, the traditional methods can be applied to determine the properties of slag, however, the change in slag composition will lead to the inaccuracy of the results. Two typical kinds of slag ESR slag with higher CaF2 and Pb smelting reduction slag with higher PbO were chosen, and melting point measurements were taken as an ex le to demonstrate the new method in practice. Weight loss measurements and evaporation test with thermogravimetric (TG) analysis, as well as high-temperature mass spectrometer (MS) tests were carried out to identify the volatiles. It was found that CaF2 and MgF2 is the main volatiles with a small amount of AlF3 to ESR slag and PbO is the main volatile with a small amount of ZnO. Based on these points and the weight loss, the slag melting points measured with traditional method and the slag chemical composition were modified to fit the melting point value. This way is proved to be feasible in theory and practice. Some suggestion for further research are proposed. The work will be of significance for both slag and molten salt with volatiles.
Publisher: Springer Science and Business Media LLC
Date: 29-11-2018
Publisher: Wiley
Date: 09-02-2015
Publisher: Wiley
Date: 20-01-2020
Abstract: Skeletal muscle contributes to ~40% of total body mass and has numerous important mechanical and metabolic roles in the body. Skeletal muscle is a major site for glucose disposal following a meal. Consequently, skeletal muscle plays an important role in postprandial blood glucose homeostasis. Over the past number of decades, research has demonstrated that insulin has an important role in vasodilating the vasculature in skeletal muscle in response to an insulin infusion (hyperinsulinaemic-euglycaemic cl ) or following the ingestion of a meal. This vascular action of insulin is pivotal for glucose disposal in skeletal muscle, as insulin-stimulated vasodilation increases the delivery of both glucose and insulin to the myocyte. Notably, in insulin-resistant states such as obesity and type 2 diabetes, this vascular response of insulin in skeletal muscle is significantly impaired. Whereas the majority of work in this field has focussed on the action of insulin alone on skeletal muscle microvascular blood flow and myocyte glucose metabolism, there is less understanding of how the consumption of a meal may affect skeletal muscle blood flow. This is in part due to complex variations in glucose and insulin dynamics that occurs postprandially-with changes in humoral concentrations of glucose, insulin, amino acids, gut and pancreatic peptides-compared to the hyperinsulinaemic-euglycaemic cl . This review will address the emerging body of evidence to suggest that postprandial blood flow responses in skeletal muscle may be a function of the nutritional composition of a meal.
Publisher: Wiley
Date: 27-12-2017
Abstract: Skeletal muscle is an important site for insulin to regulate blood glucose levels. It is estimated that skeletal muscle is responsible for ~80% of insulin-mediated glucose disposal in the post-prandial period. The classical action of insulin to increase muscle glucose uptake involves insulin binding to insulin receptors on myocytes to stimulate glucose transporter 4 (GLUT 4) translocation to the cell surface membrane, enhancing glucose uptake. However, an additional role of insulin that is often under-appreciated is its action to increase muscle perfusion thereby improving insulin and glucose delivery to myocytes. Either of these responses (myocyte and/or vascular) may be impaired in insulin resistance, and both impairments are apparent in type 2 diabetes, resulting in diminished glucose disposal by muscle. The aim of this review is to report on the growing body of literature suggesting that insulin-mediated control of skeletal muscle perfusion is an important regulator of muscle glucose uptake and that impairment of microvascular insulin action has important physiological consequences early in the pathogenesis of insulin resistance. This work was discussed at the 2015 Australian Physiological Society Symposium "Physiological mechanisms controlling microvascular flow and muscle metabolism".
Publisher: National Library of Serbia
Date: 2022
Abstract: In hemisphere point temperature (Thp) measurement of continuous casting mold flux, the evaporation of volatiles under high temperature will have a strong impact on the results. Based on the comprehensive analysis of hemisphere point method and its influencing factors, the corresponding volatile-containing mold flux and non-volatile mold flux were selected to get Thp with different heating rates. Combined with the Thp measurement and TG-DSC results, the effect of relevant factors during measuring process were analysed and the way to characterize and evaluate the effects were suggested. Furthermore, an improved method of mold flux melting point test was put forward. The results showed that for non-volatile mold flux, the temperature hysteresis had a greater effect than heat transfer delay and fractional melting. As for the mold flux with volatile, the effect of evaporation was greater than other factors. Traditional hemisphere-point method is no longer suitable for the volatile mold flux. In order to get through this problem, improved methods were proposed. One is measuring Thp traditional way, correcting the composition at the Thp, and corresponding Thp with the corrected composition. Another is taking the initial composition, revising the hemispherical point temperature Thp, and matching the revised Thp with the initial composition.
Publisher: Public Library of Science (PLoS)
Date: 11-06-2012
Publisher: American Physiological Society
Date: 05-2023
DOI: 10.1152/PHYSIOL.2023.38.S1.5733931
Abstract: The skeletal muscle microvasculature is a key regulator of peripheral resistance and plays a major role in determining muscle function. In insulin resistance and type 2 diabetes (T2D), blood flow is disrupted contributing to metabolic dysfunction. Pericytes are contractile cells known to regulate capillary diameter and microvascular blood flow in several organs, however little is known about their role in skeletal muscle. In this study, we developed a novel mouse model of T2D to characterize pericytes in healthy, insulin resistant and T2D skeletal muscle.Male Tg(Cspg4-DsRed.T1)1Akik/J mice were allocated to control diet (CD 6% fat wt/wt, n=5) or high fat diet (HFD 23% fat wt/wt, n=17) for 17wks to model insulin resistance. To model T2D, we infused streptozotocin (STZ) across 14 days using osmotic mini-pumps to generate moderate (MOD, 200mg/kgSTZ, n=5) and severe (SEV, 250-300mg/kgSTZ, n=7) hyperglycaemia. In week 17, mice underwent a 2hr glucose tolerance test (GTT 2.0g/kg IP glucose) after which mice were euthanized and cardiac perfused with 4% paraformaldehyde. The gastrocnemius and soleus were excised, processed for staining, and imaged. HFD mice were obese (CD 33.0±3.5, HFD 38.7±4.1g, p=0.011) and had elevated fasting glucose regardless of STZ dose (CD 9.6±0.9, HFD 14.7±5.1mmol/L, p=0.036). HFD mice had elevated plasma insulin (CD 166±18, HFD 242±109pmol/L, p=0.003) which was reduced to CD levels with STZ (MOD 99±44, SEV 126±46pmol/L, p .001 vs HFD). HFD and STZ induced a stepwise increase in blood glucose at the end of the 2hr GTT (CD 11.0±0.9, HFD 15.9±3.4, MOD 23.5±3.7, SEV 31.2±2.6mmol/L, p .001 for group effect). Although HFD did not change capillary density in the gastrocnemius (CD 1311±190, HFD 1263±200cap/mm2, p=0.641), capillary density was reduced in MOD (1158±315cap/mm2, p=0.007 vs HFD) and increased in SEV (1553±174cap/mm2, p=0.035 vs HFD). There was no change in pericyte density in the gastrocnemius (CD 61±21 vs HFD 63±22 vs MOD 64±15 vs SEV 81±27cells/mm2, p=0.484 for group effect). Similarly, pericyte density in the soleus was unchanged between CD (175±43 cells/mm2), HFD (147±18 cells/mm2) and MOD (118±25 cells/mm2). In contrast, SEV had a ~40% increase in pericyte density compared to all other groups (SEV 242±36cells/mm2, p .05). Perhaps most importantly, we observed distinct changes in pericyte morphology in both muscles in the HFD, MOD and SEV mice compared with CD mice. These changes include swelling and fragmentation of pericyte cytoplasmic processes that normally cover 95% of skeletal muscle capillaries.In summary, changes in pericyte density and morphology occur in insulin resistance and T2D. Given microvascular dysfunction is a hallmark of insulin resistance and T2D, this work suggests pericyte damage may contribute to blood flow dysregulation and the progression of disease. Further work is needed to understand the functional consequences of pericyte changes to skeletal muscle health in insulin resistance and T2D. This work has been supported by the Tasmanian School of Medicine and the University of Tasmania. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.
Publisher: Elsevier BV
Date: 09-2017
DOI: 10.1016/J.ULTRASMEDBIO.2017.05.012
Abstract: Most methods of assessing flowmotion (rhythmic oscillation of blood flow through tissue) are limited to small sections of tissue and are invasive in tissues other than skin. To overcome these limitations, we adapted the contrast-enhanced ultrasound (CEUS) technique to assess microvascular flowmotion throughout a large region of tissue, in a non-invasive manner and in real time. Skeletal muscle flowmotion was assessed in anaesthetised Sprague Dawley rats, using CEUS and laser Doppler flowmetry (LDF) for comparison. Wavelet transformation of CEUS and LDF data was used to quantify flowmotion. The α-adrenoceptor antagonist phentolamine was infused to predictably blunt the neurogenic component of flowmotion. Both techniques identified similar flowmotion patterns, validating the use of CEUS to assess flowmotion. This study demonstrates for the first time that the novel technique of CEUS can be adapted for determination of skeletal muscle flowmotion in large regions of skeletal muscle.
Publisher: Wiley
Date: 16-03-2023
Abstract: SnO 2 is a theoretically excellent transformed anode material with high theoretical capacity for SIBs. However, SnO 2 faces serious volume effect and high resistance, which greatly damages its electrochemical performance. Given that, the SnS−SnO 2 heterostructures is constructed with special internal electric field, which is beneficial to promote the transfer ability of sodium ions. Besides, the graphene oxide (GO) modification is carried out to isolate the intrinsic materials from direct contact with electrolyte, and alleviate volume expansion of the anode, ultimately promote the electrochemical performance. Furthermore, the structure and the conductivity characteristics of SnS, SnO 2 , SnS−SnO 2 and SnS−SnO 2 @ GO are simulated respectively by first principles and are compared with the correspondence experiment results to verify the accuracy of established models. Owing to the special p‐n junction in SnS−SnO 2 @GO heterostructures, the resistance of SnS−SnO 2 @GO can be reduced to 36.23 Ω, much lower than that of SnO 2 (Rct=341.9 Ω). Notably, the combination of GO has effectively alleviated the volume expansion of SnS−SnO 2 @GO electrodes, and present excellent capacity higher than 384.7 mAh g −1 after 100 cycles. Thus, the efficient synthesis of SnS−SnO 2 @GO heterostructure electrodes with excellent performance for sodium storage is expected to provide valuable direction for SIBs anode materials.
Publisher: MDPI AG
Date: 10-02-2020
DOI: 10.3390/MIN10020149
Abstract: To improve the conditions of extracting iron from nickel smelting residues, the composition modulating from FexO-SiO2-CaO-MgO-“NiO” slag source for matte smelting using high MgO nickel sulfide concentrate was carried out. Based on the molecular dynamics simulation and experimental characterization, the effect of CaO content in nickel slags on the physicochemical properties, the microstructure evolution, and the feasibility of subsequent iron extraction were analyzed. The results showed that, for nickel smelting slag with 9 wt.% MgO, 13–15 wt.% CaO and Fe/SiO2 ratio of 1.2, the melting temperature of nickel slag was lower than 1200 °C, and the viscosity was lower than 0.22 Pa·s at 1350 °C. The electric conductivity was similar to that of the industrial slag, and the interfacial tension between slag and matte was relatively large, which ensured a good separating characteristic. It not only met the requirements for the slag performances in the existing flash smelting process but also improved conditions for the subsequent iron extraction. Additionally, it could be adapted to the current situation where an increasing MgO content exists in the nickel sulfide concentrate.
Publisher: American Diabetes Association
Date: 12-2007
DOI: 10.2337/DB07-0745
Abstract: OBJECTIVE—We have previously shown in humans that local infusion of a nitric oxide synthase (NOS) inhibitor into the femoral artery attenuates the increase in leg glucose uptake during exercise without influencing total leg blood flow. However, rodent studies examining the effect of NOS inhibition on contraction-stimulated skeletal muscle glucose uptake have yielded contradictory results. This study examined the effect of local infusion of an NOS inhibitor on skeletal muscle glucose uptake (2-deoxyglucose) and capillary blood flow (contrast-enhanced ultrasound) during in situ contractions in rats. RESEARCH DESIGN AND METHODS—Male hooded Wistar rats were anesthetized and one hindleg electrically stimulated to contract (2 Hz, 0.1 ms) for 30 min while the other leg rested. After 10 min, the NOS inhibitor NG-nitro-l-arginine methyl ester (l-NAME) (arterial concentration of 5 μmol/l) or saline was infused into the epigastric artery of the contracting leg. RESULTS—Local NOS inhibition had no effect on blood pressure, heart rate, or muscle contraction force. Contractions increased (P & 0.05) skeletal muscle NOS activity, and this was prevented by l-NAME infusion. NOS inhibition caused a modest significant (P & 0.05) attenuation of the increase in femoral blood flow during contractions, but importantly there was no effect on capillary recruitment. NOS inhibition attenuated (P & 0.05) the increase in contraction-stimulated skeletal muscle glucose uptake by ∼35%, without affecting AMP-activated protein kinase (AMPK) activation. CONCLUSIONS—NOS inhibition attenuated increases in skeletal muscle glucose uptake during contraction without influencing capillary recruitment, suggesting that NO is critical for part of the normal increase in skeletal muscle fiber glucose uptake during contraction.
Publisher: Elsevier BV
Date: 10-2023
Publisher: Informa UK Limited
Date: 22-08-2019
Publisher: Johnson Matthey
Date: 07-2020
DOI: 10.1595/205651320X15899814766688
Abstract: The cathodes of spent ternary lithium-ion batteries (LIBs) are rich in nonferrous metals, such as lithium, nickel, cobalt and manganese, which are important strategic raw materials and also potential sources of environmental pollution. Finding ways to extract these valuable metals cleanly and efficiently from spent cathodes is of great significance for sustainable development of the LIBs industry. In the light of low energy consumption, ‘green’ processing and high recovery efficiency, this paper provides an overview of different recovery technologies to recycle valuable metals from cathode materials of spent ternary LIBs. Development trends and application prospects for different recovery strategies for cathode materials from spent ternary LIBs are also predicted. We conclude that a highly economic recovery system: alkaline solution dissolution/calcination pretreatment → H 2 SO 4 leaching → H 2 O 2 reduction → coprecipitation regeneration of nickel cobalt manganese (NCM) will become the dominant stream for recycling retired NCM batteries. Furthermore, emerging advanced technologies, such as deep eutectic solvents (DESs) extraction and one‐step direct regeneration/recovery of NCM cathode materials are preferred methods to substitute conventional regeneration systems in the future.
Publisher: Springer Science and Business Media LLC
Date: 14-03-2019
Publisher: Wiley
Date: 06-2009
Publisher: Elsevier BV
Date: 09-2016
Publisher: National Library of Serbia
Date: 2020
Abstract: Volatilization causes measurement deviations of physicochemical properties for volatiles-containing slag at high temperature. Hence, investigating the degree of volatilization and identifying the volatilization mechanism and deviation rules are crucial to improve the accuracy of the measured properties. Here, PbO-FeOx-CaO-SiO2-ZnO slag system was selected as a research subject. The volatile characteristics and non-isothermal intrinsic kinetic models of high-temperature volatilization for lead slag were established by thermogravimetric analysis (TGA), and the volatilization mechanism and deviation in the measured properties were determined by analyzing the phase and chemical composition of the residues. In addition, experimental measurements of the melting temperature/ viscosity were compared with theoretically calculated results. The volatilization of PbO decreased the lead-containing phase, but increased the amount of precipitated spinel phase, which led to the deviation in the measured physicochemical properties of the studied slags. The volatilization kinetics for PbO in the slags followed three-dimensional diffusion. The diffusion of PbO gas from PbO-FeOx-CaO-SiO2-ZnO slag was the restrictive step of volatile reaction, and mechanism function was g(?)=1-(1-?)1?3. Moreover, during the slag properties measurement at high temperatures, a high heating rate and protective gas can be used to reduce volatilization of lead slag and avoid consequent properties deviation.
Publisher: American Diabetes Association
Date: 02-02-2009
DOI: 10.2337/DB08-0775
Abstract: The cytokine interleukin-6 (IL-6) stimulates AMP-activated protein kinase (AMPK) and insulin signaling in skeletal muscle, both of which result in the activation of endothelial nitric oxide synthase (eNOS). We hypothesized that IL-6 promotes endothelial cell signaling and capillary recruitment in vivo, contributing to increased glucose uptake. The effect of IL-6 with and without insulin on AMPK, insulin, and eNOS signaling in and nitric oxide (NO) release from human aortic endothelial cells (HAECs) was examined. The physiological significance of these in vitro signaling events was assessed by measuring capillary recruitment in rats during control and euglycemic-hyperinsulinemic cl s with or without IL-6 infusion. IL-6 blunted increases in insulin signaling, eNOS phosphorylation (Ser1177), and NO production and reduced phosphorylation of AMPK in HAEC in vitro and capillary recruitment in vivo. In contrast, IL-6 increased Akt phosphorylation (Ser473) in hindlimb skeletal muscle and enhanced whole-body glucose disappearance and glucose uptake during the cl . The differences in endothelial cell and skeletal muscle signaling were mediated by the cell-specific, additive effects of IL-6 and insulin because this treatment markedly increased tumor necrosis factor (TNF)-α protein expression in HAECs without any effect on TNF-α in skeletal muscle. When HAECs were incubated with a TNF-α–neutralizing antibody, the negative effects of IL-6 on eNOS signaling were abolished. In the presence of insulin, IL-6 contributes to aberrant endothelial cell signaling because of increased TNF-α expression.
Publisher: Wiley
Date: 12-01-2015
Publisher: American Diabetes Association
Date: 07-07-2017
DOI: 10.2337/DC16-2750
Abstract: Insulin increases glucose disposal in part by enhancing microvascular blood flow (MBF) and substrate delivery to myocytes. Insulin’s microvascular action is impaired with insulin resistance and type 2 diabetes. Resistance training (RT) improves glycemic control and insulin sensitivity, but whether this improvement is linked to augmented skeletal muscle microvascular responses in type 2 diabetes is unknown. Seventeen (11 male and 6 female 52 ± 2 years old) sedentary patients with type 2 diabetes underwent 6 weeks of whole-body RT. Before and after RT, participants who fasted overnight had clinical chemistries measured (lipids, glucose, HbA1c, insulin, and advanced glycation end products) and underwent an oral glucose challenge (OGC) (50 g × 2 h). Forearm muscle MBF was assessed by contrast-enhanced ultrasound, skin MBF by laser Doppler flowmetry, and brachial artery flow by Doppler ultrasound at baseline and 60 min post-OGC. A whole-body DEXA scan before and after RT assessed body composition. After RT, muscle MBF response to the OGC increased, while skin microvascular responses were unchanged. These microvascular adaptations were accompanied by improved glycemic control (fasting blood glucose, HbA1c, and glucose area under the curve [AUC] during OGC) and increased lean body mass and reductions in fasting plasma triglyceride, total cholesterol, advanced glycation end products, and total body fat. Changes in muscle MBF response after RT significantly correlated with reductions in fasting blood glucose, HbA1c, and OGC AUC with adjustment for age, sex, % body fat, and % lean mass. RT improves OGC-stimulated muscle MBF and glycemic control concomitantly, suggesting that MBF plays a role in improved glycemic control from RT.
Publisher: Wiley
Date: 21-11-2020
Abstract: The matching of capillary blood flow to metabolic rate of the cells within organs and tissues is a critical microvascular function which ensures appropriate delivery of hormones and nutrients, and the removal of waste products. This relationship is particularly important in tissues where local metabolism, and hence capillary blood flow, must be regulated to avoid a mismatch between nutrient demand and supply that would compromise normal function. The consequences of a mismatch in microvascular blood flow and metabolism are acutely apparent in the brain and heart, where a sudden cessation of blood flow, for ex le following an embolism, acutely manifests as stroke or myocardial infarction. Even in more resilient tissues such as skeletal muscle, a short-term mismatch reduces muscle performance and exercise tolerance, and can cause intermittent claudication. In the longer-term, a microvascular-metabolic mismatch in skeletal muscle reduces insulin-mediated muscle glucose uptake, leading to disturbances in whole-body metabolic homeostasis. While the notion that capillary blood flow is fine-tuned to meet cellular metabolism is well accepted, the mechanisms that control this function and where and how different parts of the vascular tree contribute to capillary blood flow regulation remain poorly understood. Here, we discuss the emerging evidence implicating pericytes, mural cells that surround capillaries, as key mediators that match tissue metabolic demand with adequate capillary blood flow in a number of organs, including skeletal muscle.
Publisher: Springer Science and Business Media LLC
Date: 23-12-2007
DOI: 10.1007/S00125-006-0525-8
Abstract: Plasma levels of endothelin-1 are frequently elevated in patients with hypertension, obesity and type 2 diabetes. We hypothesise that this vasoconstrictor may prevent full perfusion of muscle, thereby limiting delivery of insulin and glucose and contributing to insulin resistance. The acute effects of endothelin-1 on insulin-mediated haemodynamic and metabolic effects were examined in rats in vivo. Endothelin-1 (50 pmol min(-1) kg(-1) for 2.5 h) was infused alone, or 30 min prior to a hyperinsulinaemic-euglycaemic insulin cl (10 mU min(-1) kg(-1) for 2 h). Insulin cl s (10 or 15 mU min(-1) kg(-1)) were performed after 30 min of saline infusion. Endothelin-1 infusion alone increased plasma endothelin-1 11-fold (p < 0.05) and blood pressure by 20% (p < 0.05). Endothelin-1 alone had no effect on femoral blood flow, capillary recruitment or glucose uptake, but endothelin-1 with 10 mU min(-1) kg(-1) insulin caused a decrease in insulin clearance from 0.35 +/- 0.6 to 0.19 +/- 0.02 ml/min (p = 0.02), resulting in significantly higher plasma insulin levels (10 mU min(-1) kg(-1) insulin: 2,120 +/- 190 pmol/l endothelin-1 + 10 mU min(-1)kg(-1) insulin: 4,740 +/- 910 pmol/l), equivalent to 15 mU min(-1) kg(-1) insulin alone (4,920 +/- 190 pmol/l). The stimulatory effects of equivalent doses of insulin on femoral blood flow, capillary recruitment and glucose uptake were blocked by endothelin-1. Endothelin-1 blocks insulin's haemodynamic effects, particularly capillary recruitment, and is associated with decreased muscle glucose uptake and glucose infusion rate. These findings suggest that elevated endothelin-1 levels may contribute to insulin resistance of muscle by increasing vascular resistance and limiting insulin and glucose delivery.
Publisher: Springer Science and Business Media LLC
Date: 07-2021
Publisher: Elsevier BV
Date: 10-2022
DOI: 10.1016/J.SLEH.2022.06.001
Abstract: The physiological impact of transitioning from full-time study to work in occupations that involve high-stress environments and shift work may plausibly impact sleep patterns and quality. There are limited studies focusing on the transition to shift work in graduate paramedics. This study aimed to assess early metabolic markers of health, activity, and sleep quality during the first 5 months of rostered shift work in a cohort of 28 graduate paramedics. Participants were tested for 4-week blocks before starting shift work (baseline), and during their first and fifth month of shift work. In each block, sleep and activity levels were monitored 24 h/day (workdays and nonworking days) using a wrist-worn actigraph. During shift work, the number of sleep episodes increased by 16.7% (p = .02) and self-reporting of poor sleep quality increased by 35.4% (p = .05) however, overall sleep quantity and sleep efficiency did not differ. Sleep metrics recorded during nonwork days were not different to baseline with exception of reduced sleep duration recorded the night before returning to work (5.99 ± 1.66 hours Month 1 5.72 ± 1.06 hours Month 5). Sedentary behavior increased by 4.8% across the study, attributable to a significant decline in light exercise (p = .05). No changes were recorded in vigorous physical activity, average steps recorded per day, fasting blood glucose levels, systolic and diastolic blood pressure, weight, or waist circumference. These results warrant further large-scale and longitudinal studies to gauge any physiological implications for ongoing paramedic health.
Publisher: MDPI AG
Date: 07-09-2017
DOI: 10.3390/NU9090985
Abstract: Both dietary fat and vitamin D deficiency have been linked with increased incidence of non-alcoholic fatty liver disease and insulin resistance. While sex differences in disease prevalence and severity are well known, the impact on disease pathogenesis remains unclear. To further explore the effect of these exposures on metabolic function, C57BL/6 male and female mice were weaned onto one of four diets low fat vitamin D replete, low fat vitamin D deficient, or two high fat diets, one vitamin D replete and one deficient. Visceral fat, hepatic adiposity, and insulin resistance were measured after five and a half weeks. Vitamin D deficiency, independent of dietary fat, increased hepatic fat accumulation in both sexes (p = 0.003), although did not increase hepatic expression of interleukin-6 (p = 0.92) or tumor necrosis factor-α (p = 0.78). Males were observed to have greater insulin resistance (glucose area under the curve: p 0.001, homeostatic model assessment for insulin resistance: p = 0.046), and have greater visceral adiposity (p 0.001), while female mice had greater hepatic fat accumulation (p 0.001). This study is the first to demonstrate vitamin D deficiency alone can cause hepatic accumulation while also being the first to observe higher liver fat percentages in female mice.
Publisher: Wiley
Date: 05-01-2015
Publisher: CSIRO Publishing
Date: 2016
DOI: 10.1071/RDV28N2AB23
Abstract: The morphology (spherical and without cristae) and metabolism (lowly functional) of mitochondria in early embryos and other rapidly proliferating cells exhibit a Warburg effect (WE)-like metabolism. A hallmark of the WE is the predominate use of glycolysis for energy production as opposed to the tricarboxylic acid cycle used by differentiated cells. Additionally, increased signalling of the PI3K pathway is correlated with an increase in glucose metabolism within cancer cells and is consistent with the WE. PS48 stimulates the PI3K pathway, and CPI-613 inhibits pyruvate dehydrogenase. The goal was to achieve a WE-like effect in donor cells before NT. Day 35 porcine fetal fibroblasts were treated as controls (CON, 0 μM) or with CPI (25, 50, or 100 μM) or PS48 (1, 5, 10 μM) for 7 days. Cytometry data were processed using SUMMIT software and analysed via GLM procedure of SAS (SAS Institute Inc., Cary, NC, USA) all variables were analysed for the main effect of drug concentration. Trypan blue cell viability measures were analysed using GLM. For each collection day (i.e. Day 3, 5, and 7), all variables were analysed for the main effect of treatment, duration of culture, and their interaction. All mRNA expression as measured via the ΔΔ-ct method by qPCR was analysed using CT values in GLM for the main effect of drug treatment. Total number of cells and live cells at 120 h was decreased (P ≤ 0.03) in all PS48 treatments compared with CON cells (total cells: CON = 8.95 × 106 v. PS48 treatments ≤6.98 × 106 live cells: CON = 8.39 × 106 v. PS48 treatments ≤6.50 × 106). While the percentage live cells in CPI and CON cells did not differ (P ≥ 0.09), 100 μM decreased the number of total cells and live cells from that of CON for every time point by ~50% (P ≤ 0.02), whereas the other CPI treatments 25 and 50 μM were intermediate. Expression of PDK2 was reduced with 10 μM PS48 treatment compared with CON, and 50 and 100 μM CPI treated cells (P 0.001 PS48 10 μM: 0.335 v. ≤1.012 other treatments). The CPI 100 μM and 10 μM PS48 concentrations decreased PKM M1 variant expression compared with CON and 50 μM CPI cells (P 0.001 CPI 100 μM and PS48 10 μM .44 CPI 50 μM and CON .68). To determine the mitochondrial membrane potential, JC-10 was used. The percentage of cells with high mitochondrial membrane potential decreased (P = 0.04) with PS48 treatment (PS48 treatments ≤19.6%, control = 25.6%). Treatment with CPI also decreased (P ≤ 0.01) membrane potential and the percentages of cells (high function: CPI treatments ≤12.7 v. 25.6% in control low function: CPI treatments ≥80.3 v. 74.3%). Because PS48 or CPI decrease mitochondrial membrane potential and the abundance of PKM M1, the metabolism of these potential donor cells may be more blastomere like. Experiments are underway to determine whether cells treated with PS48 or CPI will result in better development after somatic cell NT. This study was funded by Food for the 21st Century and NIH R01HD080636.
Publisher: American Physiological Society
Date: 12-2018
DOI: 10.1152/AJPENDO.00234.2018
Abstract: The microcirculation in adipose tissue is markedly impaired in type 2 diabetes (T2D). Resistance training (RT) often increases muscle mass and promotes a favorable metabolic profile in people with T2D, even in the absence of fat loss. Whether the metabolic benefits of RT in T2D are linked to improvements in adipose tissue microvascular blood flow is unknown. Eighteen sedentary people with T2D (7 women/11 men, 52 ± 7 yr) completed 6 wk of RT. Before and after RT, overnight-fasted participants had blood s led for clinical chemistries (glucose, insulin, lipids, HbA1c, and proinflammatory markers) and underwent an oral glucose challenge (OGC 50 g glucose × 2 h) and a DEXA scan to assess body composition. Adipose tissue microvascular blood volume and flow were assessed at rest and 1 h post-OGC using contrast-enhanced ultrasound. RT significantly reduced fasting blood glucose ( P = 0.006), HbA1c ( P = 0.007), 2-h glucose area under the time curve post-OGC ( P = 0.014), and homeostatic model assessment of insulin resistance ( P = 0.005). This was accompanied by a small reduction in total body fat ( P = 0.002), trunk fat ( P = 0.023), and fasting triglyceride levels ( P = 0.029). Lean mass ( P = 0.003), circulating TNF-α ( P = 0.006), and soluble VCAM-1 ( P 0.001) increased post-RT. There were no significant changes in adipose tissue microvascular blood volume or flow following RT however those who did have a higher baseline microvascular blood flow post-RT also had lower fasting triglyceride levels ( r = −0.476, P = 0.045). The anthropometric, glycemic, and insulin-sensitizing benefits of 6 wk of RT in people with T2D are not associated with an improvement in adipose tissue microvascular responses however, there may be an adipose tissue microvascular-linked benefit to fasting triglyceride levels.
Publisher: Wiley
Date: 07-06-2007
DOI: 10.1080/10739680701282796
Abstract: ABSTRACT Objective: Insulin has vascular actions within the skeletal muscle microcirculation (capillary recruitment) that enhance its own access and that of glucose to the muscle cells. Obesity and insulin resistance are associated with dysregulated vascular function within muscle and a loss of insulin‐mediated capillary recruitment. Furthermore, agents that impair insulin's vascular actions to recruit capillaries lead to acute insulin resistance in terms of muscle glucose uptake. Together these data suggest a strong connection between the loss of insulin‐mediated capillary recruitment and the development of insulin resistance. This review examines the mechanisms involved in insulin‐mediated capillary recruitment and the vascular defects associated with obesity and insulin resistance that may impair the capillary recruiting process. Understanding the mechanisms of insulin‐mediated capillary recruitment and its impairment may lead to new treatment avenues to prevent the progression of obesity to diabetes.
Publisher: Wiley
Date: 18-02-2015
No related grants have been discovered for Renee M Ross (Dwyer).