ORCID Profile
0000-0001-7922-3642
Current Organisation
Queensland University of Technology
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Research Topics
In Research Link Australia (RLA), "Research Topics" refer to ANZSRC FOR and SEO codes. These topics are either sourced from ANZSRC FOR and SEO codes listed in researchers' related grants or generated by a large language model (LLM) based on their publications.
Top 5 Research Topics
ANZSRC Field of Research (FoR)
Veterinary Medicine | Veterinary Sciences | Animal Physiology - Systems | Veterinary Pharmacology | Agricultural biotechnology | Genome Structure and Regulation | Veterinary Diagnosis and Diagnostics | Physiology | Crop and pasture protection (incl. pests diseases and weeds) | Plant cell and molecular biology | Agricultural molecular engineering of nucleic acids and proteins |
ANZSRC Socio-Economic Objective (SEO)
Horses | Animal Welfare | Expanding Knowledge in the Agricultural and Veterinary Sciences | Expanding Knowledge in the Biological Sciences |
Related Links
Publications
Differential Proteomic Expression of Equine Cardiac and Lamellar Tissue During Insulin-Induced Laminitis
Publisher: Frontiers Media SA
Date: 12-06-2020
The first experiments on the national ignition facility
Publisher: EDP Sciences
Date: 06-2006
The cresty neck score is an independent predictor of insulin dysregulation in ponies
Publisher: Public Library of Science (PLoS)
Date: 24-07-2019
Effects of an anti-IGF-1 receptor monoclonal antibody on laminitis induced by prolonged hyperinsulinaemia in Standardbred horses
Publisher: Public Library of Science (PLoS)
Date: 29-09-2020
Association between insulin dysregulation and adrenocorticotropic hormone in aged horses and ponies with no clinical signs of pituitary pars intermedia dysfunction
Publisher: Wiley
Date: 26-01-2023
DOI: 10.1111/EVJ.13925
Abstract: High concentrations of adrenocorticotropic hormone (ACTH) are used as an indicator of pituitary pars intermedia dysfunction (PPID), but other factors that may influence ACTH need to be understood, if diagnostic reference ranges for ACTH are to be used with confidence. Insulin dysregulation (ID) could be one such factor, as insulin affects pituitary hormones in other species. To test the hypothesis that a relationship exists between high insulin and high ACTH in aged ( ‐year‐old) animals with no clinical signs of PPID. A cohort study. Thirteen horses and eleven ponies (17–25 years‐old mares and geldings) were clinically examined for signs of PPID in the spring (November 2020) and autumn (April 2021). On the same day, blood s les were taken before and 2 h after an oral glucose test (OGT). Concentrations of insulin, glucose, ACTH and cortisol were measured. There was no association between ACTH and cortisol. However, there was a positive linear correlation between ACTH and post‐OGT (insulin in the autumn ( r = 0.427, p = 0.04). Two horses and six ponies had ACTH above the cut‐off value for PPID diagnosis, and of these eight animals, six also had insulin concentrations above the cut‐off value for ID. The cohort was small and thyrotropin‐releasing hormone (TRH) stimulation tests were not performed. In autumn, high ACTH was associated with ID, when no clinical signs of PPID were present. Because ACTH is used in PPID diagnosis, further work is required to understand this interaction.
Effect of environmental conditions on degree of hoof wall hydration in horses
Publisher: American Veterinary Medical Association (AVMA)
Date: 03-2012
Abstract: Objective —To determine the effect of various environmental conditions on the degree of hydration in hoof wall horn tissue from feral horses and investigate the effect of short-term foot soaking on moisture content in hoof wall and sole tissue in domestic horses. Animals —40 feral horses from 3 environments (wet and boggy [n = 10], partially flooded [20], and constantly dry desert [10]) and 6 nonferal Quarter Horses. Procedures —The percentage of moisture content of hoof wall s les from feral horses was measured in vitro. In a separate evaluation, the percentage of moisture content of hoof wall and sole tissue was measured in the dry and soaked forefeet of Quarter Horses. Results —Mean ± SD percentage of moisture content was 29.6 ± 5.1%, 29.5 ± 5.8%, and 29.5 ± 2.9% for feral horses from the wet and boggy, partially flooded, and constantly dry desert environments, respectively. Moisture content did not differ among the 3 groups, nor did it differ between dry and soaked hoof wall s les from nonferal horses. However, soaking in water for 2 hours resulted in a significant increase in the percentage of moisture content of the sole. Conclusions and Clinical Relevance —Environmental conditions do not appear to affect moisture content in the hoof wall horn. Soaking horses' feet regularly in water would be unlikely to change the degree of hydration in the hoof wall horn but may further hydrate the sole.
The oral glucose test predicts laminitis risk in ponies fed a diet high in nonstructural carbohydrates
Publisher: Elsevier BV
Date: 04-2018
DOI: 10.1016/J.DOMANIEND.2017.10.008
Abstract: The aim of this study was to investigate the relationship between laminitis development in ponies and insulin/glucose concentrations in response to the oral glucose test (OGT) and a dietary challenge high in nonstructural carbohydrates (NSCs). After undergoing an OGT (1 g dextrose/kg BW in feed), 37 ponies with 2-h serum insulin concentrations ranging from 22 to 1,133 μIU/mL were subjected to a diet challenge period (DCP), consuming 12 g NSC/kg BW/d for up to 18 d. Insulin and glucose responses were measured on day 2 of the DCP. Clinical laminitis was diagnosed by blinded experts and confirmed radiographically. Basal ACTH levels and clinical signs were assessed to investigate concurrent putative pituitary pars intermedia dysfunction (PPID). The diet induced Obel grade 1 or 2 laminitis in 14 ponies (38%). The ponies that developed laminitis had higher maximum concentrations of blood glucose (P = 0.04) and serum insulin (P = 0.02) in response to the diet. The geometric mean (95% CI) blood glucose concentration for laminitis cases was 14.9 (12.9-17.2) mM, compared to 10.7 (9.2-12.5) mM for ponies who did not develop laminitis. Similarly, the geometric mean (95% CI) for serum insulin was 396 (301-520) μIU/mL for laminitis cases, compared to 216 (148-316) μIU/mL for ponies who did not develop laminitis. Laminitis incidence was likewise associated with insulin concentrations measured during the OGT. Laminitis occurred at frequencies of 0% (0/7) if postdextrose insulin (μIU/mL) was 195 μIU/mL. Basal ACTH concentrations were above seasonally accepted reference ranges in 16/37 ponies, and 8 of these animals (50%) developed laminitis. This included all 5 ponies in the study that had clinical signs of PPID (100%). In contrast, hyperinsulinemia and laminitis occurred in only 3/11 ponies (27%) with elevated ACTH concentrations and no clinical signs of PPID (P = 0.009). Thus, laminitis occurrence was associated with higher glucose and insulin responses to both the OGT and challenge diet, and the frequency of laminitis can be predicted based on insulin and glucose hyperresponsiveness to these oral carbohydrate challenges.
Persistent digital hyperthermia over a 48h period does not induce laminitis in horses
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.TVJL.2011.09.016
Abstract: Persistent digital hyperthermia, presumably due to vasodilation, occurs during the developmental and acute stages of insulin-induced laminitis. The objectives of this study were to determine if persistent digital hyperthermia is the principal pathogenic mechanism responsible for the development of laminitis. The potent vasodilator, ATP-MgCl(2) was infused continuously into the distal phalanx of the left forefoot of six Standardbred racehorses for 48 h via intra-osseous infusion to promote persistent digital hyperthermia. The right forefoot was infused with saline solution and acted as an internal control. Clinical signs of lameness at the walk were not detected at 0 h, 24h or 48 h post-infusion. Mean ± SE hoof wall temperatures of the left forefoot (29.4 ± 0.25°C) were higher (P<0.05) than those on the right (27.5 ± 0.38°C). Serum insulin (15.0 ± 2.89 μIU/mL) and blood glucose (5.4 ± 0.22 mM) concentrations remained unchanged during the experiment. Histopathological evidence of laminitis was not detected in any horse. The results demonstrated that digital vasodilation up to 30°C for a period of 48 h does not trigger laminitis in the absence of hyperinsulinaemia. Thus, although digital hyperthermia may play a role in the pathogenesis of laminitis, it is not the sole mechanism involved.
Sweet taste receptor inhibitors: Potential treatment for equine insulin dysregulation
Publisher: Public Library of Science (PLoS)
Date: 29-06-1200
Expression of the GCG gene and secretion of active glucagon‐like peptide‐1 varies along the length of intestinal tract in horses
Publisher: Wiley
Date: 18-10-2023
DOI: 10.1111/EVJ.14020
Insulin and incretin responses to grazing in insulin‐dysregulated and healthy ponies
Publisher: Wiley
Date: 02-12-2018
DOI: 10.1111/JVIM.15363
The equine glucose-dependent insulinotropic polypeptide receptor: A potential therapeutic target for insulin dysregulation1
Publisher: Oxford University Press (OUP)
Date: 06-2017
Abstract: Metabolic disease is a significant problem that causes a range of species-specific comorbidities. Recently, a better understanding of glucose-dependent insulinotropic polypeptide (GIP) biology has led to the suggestion that inhibiting its action may attenuate obesity in several species. In horses, antagonism of GIP may also reduce hyperinsulinemia, which leads to insulin-associated laminitis, a painful comorbidity unique to this species. However, little is known about GIP in horses. The aims of this study were to examine the tissue distribution of equine GIP receptors (eGIPR), to determine whether eGIPR can be blocked using a GIP antagonist not tested previously in horses, and to establish whether there is any association between GIP concentrations and body mass in this species. Archived tissues from healthy horses were used to establish that eGIPR gene expression was strong in pancreas, heart, liver, kidney, and duodenum and absent in gluteal muscle. Pancreatic islets were isolated from fresh horse pancreas using collagenase digestion and layering through a density gradient. Islet viability was confirmed microscopically and by demonstrating that insulin production was stimulated by glucose in a concentration-dependent manner. Insulin release was also shown to be concentration-dependent with GIP up to 0.1µM, and the response to GIP was decreased ( = 0.037) by the antagonist (Pro3)GIP. As for the relationship between body mass and GIP in vivo postprandial GIP concentrations in archived plasma s les were positively correlated with body condition and cresty neck scores ( < 0.05). Thus, the eGIPR is a potential therapeutic target for insulin dysregulation and obesity in horses.
A potential role for lamellar insulin-like growth factor-1 receptor in the pathogenesis of hyperinsulinaemic laminitis
Publisher: Elsevier BV
Date: 08-2013
DOI: 10.1016/J.TVJL.2012.12.026
Abstract: The reason why a sustained high concentration of insulin induces laminitis in horses remains unclear. Cell proliferation occurs in the lamellae during insulin-induced laminitis and in other species high concentrations of insulin can activate receptors for the powerful cell mitogen, insulin-like growth factor (IGF)-1. The first aim of this study was to determine if IGF-1 receptors (IGF-1R) are activated in the hoof during insulin-induced laminitis. Gene expression for IGF-1R and the insulin receptor (InsR) was measured using qRT-PCR, in lamellar tissue from control horses and from horses undergoing a prolonged euglycaemic, hyperinsulinaemic cl (p-EHC), during the mid-developmental (24h) and acute (46 h) phases of insulin-induced laminitis. Gene expression for both receptors was decreased 13-32-fold (P<0.05) at both time-points in the insulin-treated horses. A second aim was to determine if the down-regulation of the receptor genes could be accounted for by an increase in circulating IGF-1. Serum IGF-1 was measured at 0, 10, 25 and 46 h post-treatment in horses given a p-EHC for approximately 46 h, and in matched controls administered a balanced, electrolyte solution. There was no increase in serum IGF-1 concentrations during the p-EHC, consistent with down-regulation of both receptors by insulin. Stimulation of the IGF-1R by insulin may lead to inappropriate lamellar epidermal cell proliferation and lamellar weakening, a potential mechanism for hyperinsulinaemic laminitis. Targeting this receptor may provide insights into the pathogenesis or identify a novel therapy for hyperinsulinaemic laminitis.
Science in brief: Progress in endocrinopathic laminitis research: Have we got a foothold?
Publisher: Wiley
Date: 06-02-2019
DOI: 10.1111/EVJ.13056
Evaluation of primary epidermal lamellar density in the forefeet of near-term fetal Australian feral and domesticated horses
Publisher: American Veterinary Medical Association (AVMA)
Date: 07-2011
Abstract: Objective —To investigate the density of the primary epidermal lamellae (PEL) around the solar circumference of the forefeet of near-term fetal feral and nonferal (ie, domesticated) horses. S le —Left forefeet from near-term Australian feral (n = 14) and domesticated (4) horse fetuses. Procedures —Near-term feral horse fetuses were obtained from culled mares within 10 minutes of death fetuses that had died in utero 2 weeks prior to anticipated birth date and were delivered from live Thoroughbred mares were also obtained. Following disarticulation at the carpus, the left forefoot of each fetus was frozen during dissection and data collection. In a standard section of each hoof, the stratum internum PEL density was calculated at the midline center (12 o'clock) and the medial and lateral break-over points (11 and 1 o'clock), toe quarters (10 and 2 o'clock), and quarters (4 and 6 o'clock). Values for matching lateral and medial zones were averaged and expressed as 1 density. Density differences at the 4 locations between the feral and domesticated horse feet were assessed by use of imaging software analysis. Results —In fetal domesticated horse feet, PEL density did not differ among the 4 locations. In fetal feral horse feet, PEL density differed significantly among locations, with a pattern of gradual reduction from the dorsal to the palmar aspect of the foot. The PEL density distribution differed significantly between fetal domesticated and feral horse feet. Conclusions and Clinical Relevance —Results indicated that PEL density distribution differs between fetal feral and domesticated horse feet, suggestive of an adaptation of feral horses to environment challenges.
The impact of prolonged hyperinsulinaemia on glucose transport in equine skeletal muscle and digital lamellae
Publisher: Wiley
Date: 10-09-2014
DOI: 10.1111/EVJ.12320
Abstract: An increased incidence of metabolic disease in horses has led to heightened recognition of the pathological consequences of insulin resistance. Laminitis, failure of the weightbearing digital lamellae, is an important consequence. Altered trafficking of specialised glucose transporters (GLUTs), responsible for glucose uptake, is central to the dysregulation of glucose metabolism and may play a role in the pathophysiology of laminitis. We hypothesised that prolonged hyperinsulinaemia alters the regulation of glucose transport in insulin-sensitive tissue and digital lamellae. Our objectives were to compare the relative protein expression of major GLUT isoforms in striated muscle and digital lamellae in healthy horses and during marked and moderate hyperinsulinaemia. Randomised, controlled study. Prolonged hyperinsulinaemia and lamellar damage were induced by a prolonged euglycaemic-hyperinsulinaemic cl or a prolonged glucose infusion, and results were compared with those of electrolyte-treated control animals. Protein expression of GLUTs was examined with immunoblotting. Lamellar tissue contained more GLUT1 protein than skeletal muscle (P = 0.002) and less GLUT4 than the heart (P = 0.037). During marked hyperinsulinaemia and acute laminitis (induced by the prolonged euglycaemic-hyperinsulinaemic cl ), GLUT1 protein expression was decreased in skeletal muscle (P = 0.029) but unchanged in the lamellae, while novel GLUTs (8 and 12) were increased in the lamellae (P = 0.03) but not in skeletal muscle. However, moderate hyperinsulinaemia and subclinical laminitis (induced by the prolonged glucose infusion) did not cause differential GLUT protein expression in the lamellae compared with control horses. The results suggest that lamellar tissue functions independently of insulin and that insulin resistance may not be an essential component of the aetiology of laminitis. Marked differences in GLUT expression exist between insulin-sensitive and insulin-independent tissues during metabolic dysfunction in horses. The different expression profiles of novel GLUTs during acute and subclinical laminitis may be important to disease pathophysiology and require further investigation.
Adaption of horses to a novel dynamic feeding system: Movement and behavioural responses
Publisher: Wiley
Date: 06-12-2012
DOI: 10.1111/EVJ.12002
Abstract: Many domestic horses and ponies are sedentary and obese due to confinement to small paddocks and stables and a diet of infrequent, high-energy rations. Severe health consequences can be associated with this altered lifestyle. The aims of this study were to investigate the ability of horses to learn to use a dynamic feeder system and determine the movement and behavioural responses of horses to the novel system. A dynamic feed station was developed to encourage horses to exercise in order to access ad libitum hay. Five pairs of horses (n = 10) were studied using a randomised crossover design with each pair studied in a control paddock containing a standard hay feeder and an experimental paddock containing the novel hay feeder. Horse movement was monitored by a global positioning system (GPS) and horses observed and their ability to learn to use the system and the behavioural responses to its use assessed. With initial human intervention all horses used the novel feeder within 1 h. Some aggressive behaviour was observed between horses not well matched in dominance behaviour. The median distance walked by the horses was less (P = 0.002) during a 4 h period (117 [57-185] m) in the control paddock than in the experimental paddock (630 [509-719] m). The use of an automated feeding system promotes increased activity levels in horses housed in small paddocks, compared with a stationary feeder. The novel feeder system may have application in the husbandry of horses and ponies kept in small paddocks by encouraging a natural pattern of exercise without human intervention and an ad libitum diet of hay. This may improve the health and welfare of horses.
Histological and morphometric lesions in the pre-clinical, developmental phase of insulin-induced laminitis in Standardbred horses
Publisher: Elsevier BV
Date: 03-2013
DOI: 10.1016/J.TVJL.2012.07.003
Abstract: Lamellar pathology in experimentally-induced equine laminitis associated with euglycaemic hyperinsulinaemia is substantial by the acute, clinical phase (∼48h post-induction). However, lamellar pathology of the developmental, pre-clinical phase requires evaluation. The aim of this study was to analyse lamellar lesions both qualitatively and quantitatively, 6, 12 and 24h after the commencement of hyperinsulinaemia. Histological and histomorphometrical analyses of lamellar pathology at each time-point included assessment of lamellar length and width, epidermal cell proliferation and death, basement membrane (BM) pathology and leucocyte infiltration. Archived lamellar tissue from control horses and those with acute, insulin-induced laminitis (48h) was also assessed for cellular proliferative activity by counting the number of cells showing positive nuclear immuno labelling for TPX2. Decreased secondary epidermal lamellar (SEL) width and increased histomorphological evidence of SEL epidermal basal (and supra-basal) cell death occurred early in disease progression (6h). Increased cellular proliferation in SELs, infiltration of the dermis with small numbers of leucocytes and BM damage occurred later (24 and 48h). Some lesions, such as narrowing of the SELs, were progressive over this time period (6-48h). Cellular pathology preceded leucocyte infiltration and BM pathology, indicating that the latter changes may be secondary or downstream events in hyperinsulinaemic laminitis.
Continuous intravenous infusion of glucose induces endogenous hyperinsulinaemia and lamellar histopathology in Standardbred horses
Publisher: Elsevier BV
Date: 03-2012
DOI: 10.1016/J.TVJL.2011.07.007
Abstract: Endocrinopathic laminitis is frequently associated with hyperinsulinaemia but the role of glucose in the pathogenesis of the disease has not been fully investigated. This study aimed to determine the endogenous insulin response to a quantity of glucose equivalent to that administered during a laminitis-inducing, euglycaemic, hyperinsulinaemic cl , over 48 h in insulin-sensitive Standardbred racehorses. In addition, the study investigated whether glucose infusion, in the absence of exogenous insulin administration, would result in the development of clinical and histopathological evidence of laminitis. Glucose (50% dextrose) was infused intravenously at a rate of 0.68 mL/kg/h for 48 h in treated horses (n=4) and control horses (n=3) received a balanced electrolyte solution (0.68 mL/kg/h). Lamellar histology was examined at the conclusion of the experiment. Horses in the treatment group were insulin sensitive (M value 0.039±0.0012 mmol/kg/min and M-to-I ratio (100×) 0.014±0.002) as determined by an approximated hyperglycaemic cl . Treated horses developed glycosuria, hyperglycaemia (10.7±0.78 mmol/L) and hyperinsulinaemia (208±26.1 μIU/mL), whereas control horses did not. None of the horses became lame as a consequence of the experiment but all of the treated horses developed histopathological evidence of laminitis in at least one foot. Combined with earlier studies, the results showed that laminitis may be induced by either insulin alone or a combination of insulin and glucose, but that it is unlikely to be due to a glucose overload mechanism. Based on the histopathological data, the potential threshold for insulin toxicity (i.e., laminitis) in horses may be at or below a serum concentration of ∼200 μIU/mL.
Equine hyperinsulinemia: investigation of the enteroinsular axis during insulin dysregulation
Publisher: American Physiological Society
Date: 2016
DOI: 10.1152/AJPENDO.00362.2015
Abstract: Compared with some other species, insulin dysregulation in equids is poorly understood. However, hyperinsulinemia causes laminitis, a significant and often lethal disease affecting the pedal bone/hoof wall attachment site. Until recently, hyperinsulinemia has been considered a counterregulatory response to insulin resistance (IR), but there is growing evidence to support a gastrointestinal etiology. Incretin hormones released from the proximal intestine, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide, augment insulin secretion in several species but require investigation in horses. This study investigated peripheral and gut-derived factors impacting insulin secretion by comparing the response to intravenous (iv) and oral d-glucose. Oral and iv tests were performed in 22 ponies previously shown to be insulin dysregulated, of which only 15 were classified as IR (iv test). In a more detailed study, nine different ponies received four treatments: d-glucose orally, d-glucose iv, oats, and commercial grain mix. Insulin, glucose, and incretin concentrations were measured before and after each treatment. All nine ponies showed similar iv responses, but five were markedly hyperresponsive to oral d-glucose and four were not. Insulin responsiveness to oral d-glucose was strongly associated with blood glucose concentrations and oral glucose bioavailability, presumably driven by glucose absorption/distribution, as there was no difference in glucose clearance rates. Insulin was also positively associated with the active amide of GLP-1 following d-glucose and grain. This study has confirmed a functional enteroinsular axis in ponies that likely contributes to insulin dysregulation that may predispose them to laminitis. Moreover, iv tests for IR are not reliable predictors of the oral response to dietary nonstructural carbohydrate.
The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity
Publisher: Elsevier BV
Date: 04-2011
DOI: 10.1016/J.VETIMM.2011.01.013
Abstract: Metalloproteinases have been implicated in the pathogenesis of equine laminitis and other inflammatory conditions, through their role in the degradation and remodelling of the extracellular matrix environment. Matrix metalloproteinases (MMPs) and their inhibitors are present in normal equine lamellae, with increased secretion and activation of some metalloproteinases reported in horses with laminitis associated with systemic inflammation. It is unknown whether these enzymes are involved in insulin-induced laminitis, which occurs without overt systemic inflammation. In this study, gene expression of MMP-2, MMP-9, MT1-MMP, ADAMTS-4 and TIMP-3 was determined in the lamellar tissue of normal control horses (n=4) and horses that developed laminitis after 48 h of induced hyperinsulinaemia (n=4), using quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). Protein concentrations of MMP-2 and MMP-9 were also examined using gelatin zymography in horses subject to prolonged hyperinsulinaemia for 6h (n=4), 12h (n=4), 24h (n=4) and 48 h (n=4), and in normal control horses (n=4). The only change in gene expression observed was an upregulation of MMP-9 (p<0.05) in horses that developed insulin-induced laminitis (48 h). Zymographical analysis showed an increase (p<0.05) in pro MMP-9 during the acute phase of laminitis (48 h), whereas pro MMP-2 was present in similar concentration in the tissue of all horses. Thus, MMP-2, MT1-MMP, TIMP-3 and ADAMTS-4 do not appear to play a significant role in the pathogenesis of insulin-induced laminitis. The increased expression of MMP-9 may be associated with the infiltration of inflammatory leukocytes, or may be a direct result of hyperinsulinaemia. The exact role of MMP-9 in basement membrane degradation in laminitis is uncertain as it appears to be present largely in the inactive form.
The feral horse foot. Part A: observational study of the effect of environment on the morphometrics of the feet of 100 Australian feral horses
Publisher: Wiley
Date: 21-09-2012
DOI: 10.1111/J.1751-0813.2012.00995.X
Abstract: To better understand the morphology of, and the effect of different travel patterns and varying substrate environments on, the feral horse foot to better manage the feet of domestic horses. The left forefeet of 20 adult feral horses from each of five geographically separated populations in Australia (n = 100) were investigated. Populations were selected on the basis of substrate hardness under foot and the amount of travel typical for the population. Feet were radiographed and photographed and 40 morphometric measurements of each foot were obtained. Of the 40 parameters, 37 differed significantly (P < 0.05) among the populations, which suggested that substrate hardness and travel distance have an effect on foot morphology. Harder substrates and longer travel distances were associated with short hoof walls and minimal hoof wall flaring. Softer substrates and moderate travel distances were associated with long flared walls, similar to that of typical untrimmed feet of domestic horses. The morphology of the feral horse foot appeared to be affected by the distance travelled and by the abrasive qualities and mechanical properties of the substrate under foot. There were marked differences in some conformation parameters between the feral horses in the current study and domestic horses in previous studies. Although the conformation of the feral horse foot may have some prescriptive value, concerns regarding abnormal foot anatomy warrant further investigation.
The equine glucose-dependent insulinotropic polypeptide receptor: A potential therapeutic target for insulin dysregulation
Publisher: Oxford University Press (OUP)
Date: 2017
DOI: 10.2527/JAS2017.1468
A review of recent developments in the pharmacological prevention and treatment of endocrinopathic laminitis
Publisher: CSIRO Publishing
Date: 2020
DOI: 10.1071/AN19491
Abstract: Despite the prevalence of endocrinopathic laminitis, the pharmacologic options for preventing and treating the disease are severely limited. The present review aims to discuss the spectrum of potential therapeutic agents for the condition, ranging from early experimental compounds to agents nearing registration. There are different pharmacologic targets for, and approaches to, managing laminitis. Reducing hyperinsulinaemia is central to diminishing endocrinopathic laminitis risk, and a detailed understanding of the pathophysiology of insulin dysregulation is necessary to identify pathways that can be targeted to minimise post-prandial insulin secretion and action. This area of research is advancing rapidly, with several exciting prospects, such as sodium-dependent glucose co-transporter-2 inhibitors, on the horizon for the treatment of equine metabolic dysfunction. Drugs that directly target the lamellae and aim to reduce the damage inflicted on the lamellae as part of this condition, are not yet available. Although progress in this area of laminitis therapy is slower, improved understanding of the events that lead to lamellar failure has enabled the investigation of novel drugs that aim to prevent laminitis at the site of the lesion. Finally, a brief review is included of the directions being taken in the management of the chronic and acute pain that accompanies laminitis. Medications for relieving the pain associated with laminitis are currently the most-prescribed drugs for the disease, and range from simple, affordable and thoroughly tested options, such as phenylbutazone, to newer, less-understood applications such as paracetamol and gabapentin. In the future, endocrinopathic laminitis management plans will likely take a multi-faceted approach that still hinge on effective dietary management and exercise, but also include drugs that address foot pathology, pain and underlying endocrine disturbances.
Hyperinsulinemia Down-Regulates TLR4 Expression in the Mammalian Heart
Publisher: Frontiers Media SA
Date: 22-07-2014
The sodium-glucose co-transporter 2 inhibitor velagliflozin reduces hyperinsulinemia and prevents laminitis in insulin-dysregulated ponies
Publisher: Public Library of Science (PLoS)
Date: 13-09-2018
Equine Laminitis: Comparative Histopathology 48 hours after Experimental Induction with Insulin or Alimentary Oligofructose in Standardbred Horses
Publisher: Elsevier BV
Date: 11-2011
DOI: 10.1016/J.JCPA.2011.02.001
Abstract: Laminitis has many triggers and comparing the histopathology of lesions induced by different causes may help to establish whether a common mechanism or multiple pathologies are involved. The aim of this study was to describe the microscopical lesions and to quantify morphometric changes in the lamellae of horses with insulin-induced (n=4) and oligofructose (OF)-induced laminitis (n=4) compared with normal controls (n=4). Archived lamellar s les collected during two previous studies were used. Laminitis was induced within 48 h in standardbred horses with either a euglycaemic, hyperinsulinaemic cl (EHC) technique or, in a separate experiment, with an overdose of alimentary OF. Normal tissue was obtained from control horses in the EHC experiment that received a balanced electrolyte solution intravenously for 48 h. Six measurements of lamellar length and width were recorded for each hoof. Leucocyte infiltration was assessed by immunolocalization of calprotectin. All control horses exhibited normal lamellar architecture, whereas treated horses developed clinical and histopathological changes consistent with laminitis. Laminitic s les displayed lengthening and narrowing of secondary epidermal lamellae (SELs), rounded epidermal basal cell (EBC) nuclei, mitosis and apoptosis. In the fore feet of laminitic horses, the length from the end of the keratinized axis to the axial tip of the primary epidermal lamellae (PELs) was increased (P<0.05). SELs were significantly longer (P<0.05) and narrower (P<0.05) in the treated horses compared with controls. The two treated groups did not differ from each other in SEL length or width. Calprotectin expression was absent in control horses, moderate in hyperinsulinaemic horses and marked in OF-treated horses. Laminitis induced experimentally with insulin or OF results in comparable lengthening and narrowing of the SELs and elongation of the axial end of the PELs at 48 h. Immunolocalization of calprotectin indicated that hyperinsulinaemia induces less leucocyte emigration than carbohydrate overload at 48 h. The microscopical lesion of laminitis is similar, but not identical in different forms of the disease.
Morphometry and abnormalities of the feet of Kaimanawa feral horses in New Zealand
Publisher: Wiley
Date: 18-03-2010
DOI: 10.1111/J.1751-0813.2010.00554.X
Abstract: The present study investigated the foot health of the Kaimanawa feral horse population and tested the hypotheses that horses would have a large range of foot morphology and that the incidence of foot abnormality would be significantly high. Abnormality was defined as a variation from what the two veterinarian assessors considered as optimal morphology and which was considered to impact negatively on the structure and/or function of the foot. Fifteen morphometric variables were measured on four calibrated photographic views of all four feet of 20 adult Kaimanawa feral horses. Four morphometric variables were measured from the lateromedial radiographs of the left forefoot of each horse. In addition, the study identified the incidence of gross abnormality observed on the photographs and radiographs of all 80 feet. There was a large variation between horses in the morphometric dimensions, indicating an inconsistent foot type. Mean hoof variables were outside the normal range recommended by veterinarians and hoof care providers 35% of all feet had a long toe conformation and 15% had a mediolateral imbalance. Abnormalities included lateral (85% of horses) and dorsal (90% of horses) wall flares, presence of laminar rings (80% of horses) and bull-nose tip of the distal phalanx (75% of horses). Both hypotheses were therefore accepted. The Kaimanawa feral horse population demonstrated a broad range of foot abnormalities and we propose that one reason for the questionable foot health and conformation is lack of abrasive wearing by the environment. In comparison with other feral horse populations in Australia and America there may be less pressure on the natural selection of the foot of the Kaimanawa horses by the forgiving environment of the Kaimanawa Ranges. Contrary to popular belief, the feral horse foot type should not be used as an ideal model for the domestic horse foot.
Re: Recommendations from the Australian and New Zealand Equine Endocrine Group and the interpretation of plasma endogenous ACTH concentrations for the diagnosis of pituitary pars intermedia dysfunction (PPID)
Publisher: Wiley
Date: 27-08-2018
DOI: 10.1111/AVJ.12744
Equine metabolic syndrome: Role of the enteroinsular axis in the insulin response to oral carbohydrate
Publisher: Elsevier BV
Date: 04-2023
Demographic, morphologic, hormonal and metabolic factors associated with the rate of improvement from equine hyperinsulinaemia-associated laminitis
Publisher: Springer Science and Business Media LLC
Date: 18-01-2022
DOI: 10.1186/S12917-022-03149-Z
Abstract: Although several studies have investigated factors associated with the onset and occurrence of hyperinsulinaemia-associated laminitis (HAL), few have examined the factors associated with the rate of improvement during recovery from an acute bout of the disease. This observational study sought to discover if a range of demographic, morphologic, hormonal and metabolic variables are associated with the improvement rate from HAL in 37 naturally-occurring cases identified by 16 clinics across Germany. Each case was evaluated for laminitis severity on the day of inclusion in the trial (d 0), then after 4, 9, 14, 25 and 42 d. The horses were managed according to best clinical practice including restricting exercise and prescribing a diet of hay-only, for a minimum of 9 d. Blood s les were also collected during each evaluation, except on d 9, and analysed for glucose, insulin, ACTH and leptin. Based on in idual clinical laminitis scores plotted against time, most horses improved markedly within 2 weeks, with a ‘fast group’ ( n = 27) having a median (interquartile range) score on a 12-point scale of 0 (0–2) by d 14. However, there was a clear disparity within the total cohort, as ~ 1 in 4 horses demonstrated much slower improvement, with a median score of 5 (4–7) by d 14, or a marked relapse thereafter (‘slow group’, n = 10). Horses in the slow improvement group were younger (12.5 (8.8–16.3) vs 17 (14–24) yr P = 0.008), but were not more likely to be heavier, male, very fat, to have presented with a previous history of laminitis or elevated ACTH concentrations, or to be receiving pergolide treatment. Of the hormonal and metabolic parameters measured, glucose and insulin concentrations were within the normal range following transition to the hay-only diet, but were higher in the group that failed to improve quickly, with a small but significant difference being evident on d 4, 14 and 25 for glucose (11 to 16% P 0.05), and a larger difference for insulin on d 14 and 25 (51 to 55% P 0.05). There was no difference between the groups in ACTH or leptin concentrations throughout the study. The main limitations of this study were the small number of slow-improvement horses and an inability to control or measure certain variables, such as feed quality. Young age and a modest increase in blood glucose and insulin concentrations are associated with delayed laminitis improvement.
Sole depth and weight-bearing characteristics of the palmar surface of the feet of feral horses and domestic Thoroughbreds
Publisher: American Veterinary Medical Association (AVMA)
Date: 06-2011
Abstract: Objective —To determine solar load-bearing structures in the feet of feral horses and investigate morphological characteristics of the sole in feral horses and domestic Thoroughbreds. S le —Forelimbs from cadavers of 70 feral horses and 20 domestic Thoroughbreds in Australia. Procedures —Left forefeet were obtained from 3 feral horse populations from habitats of soft substrate (SS [n = 10 horses]), hard substrate (HS [10]), and a combination of SS and HS (10) and loaded in vitro. Pressure distribution was measured with a pressure plate. Sole depth was measured at 12 points across the solar plane in feet obtained from feral horses from SS (n = 20 horses) and HS (20) habitats and domestic Thoroughbreds (20). Results —Feet of feral horses from HS habitats loaded the periphery of the sole and hoof wall on a flat surface. Feral horses from HS or SS habitats had greater mean sole depth than did domestic Thoroughbreds. Sole depth was greatest peripherally and was correlated with the loading pattern. Conclusions and Clinical Relevance —The peripheral aspect of the sole in the feet of feral horses had a load-bearing function. Because of the robust nature of the tissue architecture, the hoof capsule of feral horses may be less flexible than that of typical domestic horses. The application of narrow-web horseshoes may not take full advantage of the load-bearing and force-dissipating properties of the peripheral aspect of the sole. Further studies are required to understand the effects of biomechanical stimulation on the adaptive responses of equine feet.
Reining in equine metabolic syndrome: A gluttony of challenges
Publisher: Elsevier BV
Date: 05-2013
Identification of monoclonal antibodies suitable for blocking IGF-1 receptors in the horse
Publisher: Elsevier BV
Date: 2021
Nutritional analysis of gastric contents and body condition score at a single time point in feral horses in Australia
Publisher: American Veterinary Medical Association (AVMA)
Date: 09-2011
Abstract: Objective —To determine the impact of a free-choice diet on nutritional intake and body condition of feral horses. Animals —Cadavers of 41 feral horses from 5 Australian locations. Procedures —Body condition score (BCS) was determined (scale of 1 to 9), and the stomach was removed from horses during postmortem examination. Stomach contents were analyzed for nutritional variables and macroelement and microelement concentrations. Data were compared among the locations and also compared with recommended daily intakes for horses. Results —Mean BCS varied by location all horses were judged to be moderately thin. The BCS for males was 1 to 3 points higher than that of females. Amount of protein in the stomach contents varied from 4.3% to 14.9% and was significantly associated with BCS. Amounts of water-soluble carbohydrate and ethanol-soluble carbohydrate in stomach contents of feral horses from all 5 locations were higher than those expected for horses eating high-quality forage. Some macroelement and microelement concentrations were grossly excessive, whereas others were grossly deficient. There was no evidence of ill health among the horses. Conclusions and Clinical Relevance —Results suggested that the diet for several populations of feral horses in Australia appeared less than optimal. However, neither low BCS nor trace mineral deficiency appeared to affect survival of the horses. Additional studies on food sources in these regions, including analysis of water-soluble carbohydrate, ethanol-soluble carbohydrate, and mineral concentrations, are warranted to determine the provenance of such rich sources of nutrients. Determination of the optimal diet for horses may need revision.
The effect of different grazing conditions on the insulin and incretin response to the oral glucose test in ponies
Publisher: Springer Science and Business Media LLC
Date: 16-10-2019
DOI: 10.1186/S12917-019-2088-1
Abstract: The oral glucose test (OGT) is a useful tool for diagnosing insulin dysregulation (ID) and is somewhat repeatable in ponies under consistent management. This study aimed to determine whether the insulin and incretin responses to an OGT in ponies differed after short-term access to fertilised pasture, compared to unfertilised pasture, by using a randomised, repeated measures study design. Sixteen mixed-breed ponies were classified as severely insulin-dysregulated (SD post-prandial insulin ≥80 μIU/mL) or not severely insulin-dysregulated (NSD post-prandial insulin 80 μIU/mL) using an OGT prior to the study. The ponies accessed pasture that was fertilised, or unfertilised, for 5 days (4 h/day, with supplemental hay provided at 0.7% bodyweight), with a 10 day period between phases. An OGT was performed after each phase. Glucose, insulin, active glucagon-like peptide-1 (aGLP-1), and glucose-dependent insulinotropic polypeptide (GIP) were measured in post-prandial blood s les. The volume of fertilised pasture was five-fold greater than unfertilised pasture, with % non-structural carbohydrates (NSC) similar between all forages. Consuming fertilised pasture increased ( P = 0.018) the serum insulin response to an OGT, compared to grazing unfertilised pasture. A limitation of the study was that pasture intake was unable to be quantified. Insulin responses were greater in SD, compared to NSD, ponies ( P 0.001) and remained well above the test cut-off at all times. A subset of ponies, initially screened as NSD, became (more) insulin-dysregulated after pasture access. Further, aGLP-1 was a significant predictor of insulin concentration in this cohort. Whereas some insulin-dysregulated ponies were comparatively resistant to dietary intervention, others showed markedly different OGT responses following subtle changes in their forage-based diet. This implies that mild/early ID might be unmasked by dietary change, and that dietary management is important in these ponies. However, dietary management alone may not be adequate for all cases of ID.
Preliminary analysis of the FAM174A gene suggests it lacks a strong association with equine metabolic syndrome in ponies
Publisher: Elsevier BV
Date: 07-2020
Ultrastructural examination of basement membrane pathology in horses with insulin-induced laminitis
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.DOMANIEND.2019.04.004
Abstract: The third phalanx of the equine digit is suspended within the hoof capsule by a specialized interdigitating dermoepidermal layer called the lamellae, which fails during laminitis. Pathology of the basement membrane (BM), which interfaces epidermis and dermis, is evident during acute laminitis. However, BM damage appears to be less prevalent in ponies with the insulin-associated form of laminitis. The aim of the present study was to investigate changes to the ultrastructure and morphometry of the lamellar BM in the acute phase of insulin-induced laminitis in horses. Lamellar tissue from the left forefoot of 3 horses with acute hyperinsulinemic laminitis was examined with transmission electron microscopy and compared with tissue from normal horses. Lamellar BM width and hemidesmosome (HD) density were assessed every 5 μm along ∼200 μm of secondary epidermal lamellar BM. The BM zone of treated horses was extensively disorganized with loss of uniformity of the lamina lucida and lamina densa, fragmentation and disorientation of HDs, and cytoskeletal disengagement of the HDs. The mean (±SD) lamellar BM was twice as wide in treated (0.25 ± 0.05 μm), compared with control (0.14 ± 0.02 μm), horses. The HD density (HDs/μm) was reduced by half in the treatment group (1.88 ± 0.37), compared with controls (3.6 ± 0.13). The reduced number of HDs in horses with laminitis may contribute to the weakening of the dermoepidermal junction and lamellar failure. Disassembly of HDs during excessive cellular proliferation, secondary to hyperinsulinemia, may account for HD loss. Further investigation of the underlying etiopathogenesis of BM dysfunction during hyperinsulinemic laminitis in horses may facilitate an improved understanding of the disease.
The repeatability of an oral glucose test in ponies
Publisher: Wiley
Date: 23-05-2016
DOI: 10.1111/EVJ.12579
Abstract: Insulin dysregulation can be difficult to diagnose from basal insulin and glucose concentrations, so a field-based oral glucose test (OGT) is preferred. However, the repeatability of this test has not been reported. To determine the repeatability of an in-feed OGT in ponies and examine some factors affecting the palatability of the test meal. A repeated measures, longitudinal study. An in-feed OGT was performed at 08.00 h on 3 consecutive occasions under controlled conditions in 8 mixed breed ponies. d-glucose (0.75 g/kg bwt) was dissolved in water and combined with wheat bran and lucerne chaff. Blood s les were taken before and 90, 120, 180 min and 24 h after d-glucose. The repeatability of the test was analysed with repeated measures ANOVA. Insulin and glucose responses to d-glucose were also compared to an equivalent dose of dietary carbohydrate provided with a commercial grain mixture. The overall insulin responses to the OGTs did not differ between tests. In idual insulin responses were more variable (P<0.05) than glucose responses. There was no difference in insulin concentration in post d-glucose s les over time. Insulin and glucose responses to grain and d-Glucose were not different. An OGT is reasonably repeatable in ponies. The currently recommended post-glucose s ling time point of 2 h is acceptable, with s ling at 90 min also likely to produce a consistent result. The use of an alternative carbohydrate source to d-glucose, such as a commercial grain-based product, may be a viable and more palatable option for the test.
Hyperinsulinemic Laminitis
Publisher: Elsevier BV
Date: 08-2010
DOI: 10.1016/J.CVEQ.2010.04.003
Abstract: Laminitis occurring in association with hyperinsulinemia is frequently encountered in today's equine population. New evidence suggests that hyperinsulinemia is the direct cause of this form of laminitis, rather than insulin resistance per se. The mechanism by which elevated serum insulin concentrations result in lamellar dysfunction is currently under investigation by many researchers and the use of a new insulin infusion model for investigating the pathogenesis of insulin-associated laminitis will doubtless enhance progress in this field of research. By focusing on the metabolic and vascular actions of insulin in the lamellar microenvironment, our research group is trying to gain an insight into the pathophysiological processes involved in this complex problem, in order to better understand the disease.
The efficacy and safety of velagliflozin over 16 weeks as a treatment for insulin dysregulation in ponies
Publisher: Springer Science and Business Media LLC
Date: 26-02-2019
A starch-rich treat affects enteroinsular responses in ponies
Publisher: American Veterinary Medical Association (AVMA)
Date: 12-2022
Abstract: To determine the effect of a starch-rich treat, added to the daily diet of ponies for 10 days, on enteroinsular responses to meal consumption. 10 mixed-breed adult ponies owned by Queensland University of Technology were used in the study. Six ponies were metabolically healthy, and 4 were insulin dysregulated at the start of the study, according to the results of an in-feed oral glucose test. A bread-based treat was offered twice daily for 10 days, adding 0.36 ± 0.04 g/kg body weight (BW) carbohydrates to the daily diet. Before and after treatment, the intestinal capacity for simple carbohydrate absorption was approximated with a modified D-xylose absorption test. Plasma glucagon-like peptide-2 (GLP-2), blood glucose, and serum insulin responses to eating were also measured before and after treatment. The absorption of D-xylose (area under the curve [AUC]) increased 1.6-fold ( P .001) after 10 days of eating the treat. In addition, while basal (fasted) GLP-2 concentrations were not affected, GLP-2 AUC increased 1.4-fold in response to eating ( P = .005). The treat did not change blood glucose or serum insulin concentrations, before, during, or after eating. A small amount of additional carbohydrate each day in the form of a treat can cause a measurable change in the enteroinsular responses to eating.
AICAR administration affects glucose metabolism by upregulating the novel glucose transporter, GLUT8, in equine skeletal muscle
Publisher: Elsevier BV
Date: 09-2015
DOI: 10.1016/J.TVJL.2015.05.018
Abstract: Equine metabolic syndrome is characterized by obesity and insulin resistance (IR). Currently, there is no effective pharmacological treatment for this insidious disease. Glucose uptake is mediated by a family of glucose transporters (GLUT), and is regulated by insulin-dependent and -independent pathways, including 5-AMP-activated protein kinase (AMPK). Importantly, the activation of AMPK, by 5-aminoimidazole-4-carboxamide-1-D-ribofuranoside (AICAR) stimulates glucose uptake in both healthy and diabetic humans. However, whether AICAR promotes glucose uptake in horses has not been established. It is hypothesized that AICAR administration would enhance glucose transport in equine skeletal muscle through AMPK activation. In this study, the effect of an intravenous AICAR infusion on blood glucose and insulin concentrations, as well as on GLUT expression and AMPK activation in equine skeletal muscle (quantified by Western blotting) was examined. Upon administration, plasma AICAR rapidly reached peak concentration. Treatment with AICAR resulted in a decrease (P <0.05) in blood glucose and an increase (P <0.05) in insulin concentration without a change in lactate concentration. The ratio of phosphorylated to total AMPK was increased (P <0.05) in skeletal muscle. While GLUT4 and GLUT1 protein expression remained unchanged, GLUT8 was increased (P <0.05) following AICAR treatment. Up-regulation of GLUT8 protein expression by AICAR suggests that this novel GLUT isoform plays an important role in equine muscle glucose transport. In addition, the data suggest that AMPK activation enhances pancreatic insulin secretion. Collectively, the findings suggest that AICAR acutely promotes muscle glucose uptake in healthy horses and thus its therapeutic potential for managing IR requires investigation.
Sustained, Low‐Intensity Exercise Achieved by a Dynamic Feeding System Decreases Body Fat in Ponies
Publisher: Wiley
Date: 09-2016
DOI: 10.1111/JVIM.14577
Abstract: Obesity in horses is increasing in prevalence and can be associated with insulin insensitivity and laminitis. Current treatment strategies for obesity include dietary restriction and exercise. However, whether exercise alone is effective for decreasing body fat is uncertain. Our hypothesis was that twice daily use of a dynamic feeding system for 3 months would induce sustained, low-intensity exercise thereby decreasing adiposity and improving insulin sensitivity (SI). Eight, university-owned, mixed-breed, adult ponies with body condition scores (BCS) ≥5/9 were used. Two treatments ("feeder on" or "feeder off") were administered for a 3-month period by a randomized, crossover design (n = 4/treatment). An interim equilibration period of 6 weeks at pasture separated the 2 study phases. Measurements of body mass (body weight, BCS, cresty neck score [CrNS], and morphometry), body fat (determined before and after the "feeder on" treatment only), triglycerides, and insulin sensitivity (SI combined glucose-insulin test) were undertaken before and after treatments. The dynamic feeding system induced a 3.7-fold increase in the daily distance travelled (n = 6), compared to with a stationary feeder, which significantly decreased mean BCS (6.53 ± 0.94 to 5.38 ± 1.71), CrNS (2.56 ± 1.12 to 1.63 ± 1.06) and body fat (by 4.95%). An improvement in SI did not occur in all ponies. A dynamic feeding system can be used to induce sustained (daily), low-intensity exercise that promotes weight loss in ponies. However, this exercise may not be sufficient to substantially improve SI.
Characterization of insulin and IGF-1 receptor binding in equine liver and lamellar tissue: implications for endocrinopathic laminitis
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.DOMANIEND.2018.05.008
Abstract: Although it is well established that equine laminitis can be triggered by extreme hyperinsulinemia, the mechanism of insulin action is not known. High concentrations of insulin lead to separation of the weight-bearing apparatus from the hoof wall and are associated with an increased cycle of cell death and proliferation in the lamellae. Gene expression and immunohistochemistry studies have indicated that the lamellae are sparsely populated with insulin receptors, whereas IGF-1 receptors (IGF-1R) are abundant, suggesting that the action of insulin may be mediated by insulin binding to the IGF-1R. To investigate this possibility, cell membrane fragments containing IGF-1R were extracted from the livers of 6 horses and the lamellae of >50 horses euthanized for nonresearch purposes at an abattoir. Radioligand-binding studies using
Factors Affecting the Rate and Measurement of Feed Intake for a Cereal-Based Meal in Horses
Publisher: Elsevier BV
Date: 2020
DOI: 10.1016/J.JEVS.2019.102869
Abstract: The rapid intake of high-cereal, low-roughage meals may cause gastrointestinal and behavioral disorders. We investigated some of the factors that can affect the rate of intake (ROI) in four separate studies. Study 1 investigated the effect of chaff length and addition rate on the ROI of oats. The ROI decreased as more chaff was added to the diet, attaining significance (P < .05, n = 6) at levels above 15% addition and reaching a plateau at ∼50%. This was independent of stalk length (1.4 cm vs. 4.1 cm). Study 2 showed that meal size (varying from 0.5 to 4 g/kg BW) did not affect the ROI for a cereal-based meal, nor was ROI altered by the addition of 10% molasses (n = 6). Study 3 demonstrated that ROI changed markedly over the course of a meal, commencing at an average rate of 74 g/minute for the first 5 minutes and decreasing to 15.8 g/minute after 30 minutes (n = 6). Study 4 examined the effects of breed, BW, exercise, and gender in 71 horses. In Clydesdales, BW affected ROI (P < .05), and Clydesdales had a faster ROI than Thoroughbreds of similar BW (81.8 ± 6.8 vs. 66.0 ± 3.35 g/minute P < .05). Exercise level, age, and gender did not impact ROI significantly. The results highlight the effectiveness of feeding chaff to slow ROI and demonstrate the need for a standardized protocol if ROI is to be compared between different studies.
Glucagon-like peptide-1, insulin-like growth factor-1, and adiponectin in insulin-dysregulated ponies: effects of feeding a high nonstructural carbohydrate diet and association with prospective lamini
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.DOMANIEND.2019.106397
Abstract: Endocrinopathic laminitis, related to equine metabolic syndrome and insulin dysregulation, causes marked pain and suffering in horses and represents a substantial cost to the horse industry. This study investigated the effect of feeding a diet high in nonstructural carbohydrates on concentrations of active glucagon-like peptide-1 (aGLP-1), total insulin-like growth factor-1 (IGF-1), and high-molecular-weight (HMW) adiponectin, in insulin-dysregulated ponies. Thirty-seven ponies were challenged with this diet for up to 18 d to induce hyperinsulinemia. Hormone concentrations were measured in selected s les on day 2 of the diet challenge period, over 4 h after feeding. Fourteen of the ponies developed mild laminitis induced by the diet challenge. Insulin and glucose responses to the diet have been reported previously. Feeding increased the concentrations of aGLP-1 (P < 0.05) and HMW adiponectin (P < 0.001), but there was no difference between the laminitic and nonlaminitic groups for either hormone. Concentrations of IGF-1 and insulin were inversely related, with IGF-1 being 32% lower in hyperinsulinemic/laminitic ponies compared with nonlaminitic ponies (P = < 0.05). These results indicate that unlike insulin and possibly IGF-1, concentrations of aGLP-1 and HMW adiponectin do not have a strong association with, or play a major role in, the pathogenesis of equine laminitis.
A “modified Obel” method for the severity scoring of (endocrinopathic) equine laminitis
Publisher: PeerJ
Date: 07-06-2019
DOI: 10.7717/PEERJ.7084
Abstract: Laminitis is a common equine disease characterized by foot pain, and is commonly diagnosed using a five-grade Obel system developed in 1948 using sepsis-related cases. However, endocrinopathic laminitis is now the most common form of the disease and clinical signs may be mild, or spread across two Obel grades. This paper describes a modified method which assigns scores to discreet clinical signs, providing a wider scale suitable for use in a research setting. The “modified Obel” method was developed using an iterative process. First, a prototype method was developed during the detailed observation of 37 ponies undergoing a laminitis induction experiment. The final method was refined and validated using video footage taken during the induction study and from a clinical trial of naturally occurring endocrinopathic laminitis cases. The Obel method was deconstructed and key laminitis signs were evaluated to develop a three-stage, five criteria method that employs a severity scale of 0–12. Veterinarians ( n = 28) were recruited to watch and assess 15 video recordings of cases of varying severity, using the Obel and “modified Obel” methods. The inter-observer agreement (reproducibility) was determined using Kendall’s coefficient of concordance (Kendall W ) and Krippendorf’s alpha reliability coefficient. A total of 14 veterinarians repeated the exercise 2–4 weeks after their original assessment, to determine intra-observer agreement (repeatability), assessed using a weighted kappa statistic ( kw ). Agreement between methods was calculated by converting all “modified Obel” scores to Obel grades and calculating the mean and distribution of the differences. The “modified Obel” and Obel methods showed excellent and similar inter-observer agreement based on the Kendall W value (0.87, P 0.001 vs. 0.85, P 0.001) and Krippendorf’s alpha (95% CI) value (0.83 [0.53–0.90] vs. 0.77 [0.55–0.85]). Based on the kw value, the “modified Obel” method also had substantial repeatability, although slightly less than the Obel method, (0.80 vs. 0.91). Excellent agreement between the methods was found, with the mean difference (95% CI), comparing the Obel grade, with the “modified Obel” score converted to an Obel grade, being −0.12 (−0.19 to −0.06) grades. The Obel and converted “modified Obel” grades were identical 62% of the time (259/420) and a difference of one grade (higher or lower) occurred in 35% of cases (148/420). Both methods show excellent agreement, reproducibility and repeatability when used to diagnose endocrinopathic laminitis. The “modified Obel” method is a three-step examination process for severity-scoring of endocrinopathic laminitis, initially proposed for use within a research setting. When using the modified method a diagnosis of laminitis also requires clinical acumen. The allocation of scores for specific clinical signs should be particularly useful in research trials monitoring laminitis recovery.
The feral horse foot. Part B: radiographic, gross visual and histopathological parameters of foot health in 100 Australian feral horses
Publisher: Wiley
Date: 2013
DOI: 10.1111/AVJ.12017
Abstract: It has been proposed that the feral horse foot is a benchmark model for foot health in horses. However, the foot health of feral horses has not been formally investigated. To investigate the foot health of Australian feral horses and determine if foot health is affected by environmental factors, such as substrate properties and distance travelled. Twenty adult feral horses from five populations (n = 100) were investigated. Populations were selected on the basis of substrate hardness and the amount of travel typical for the population. Feet were radiographed and photographed, and digital images were surveyed by two experienced assessors blinded to each other's assessment and to the population origin. Lamellar s les from 15 feet from three populations were investigated histologically for evidence of laminitis. There was a total of 377 gross foot abnormalities identified in 100 left forefeet. There were no abnormalities detected in three of the feet surveyed. Each population had a comparable prevalence of foot abnormalities, although the type and severity of abnormality varied among populations. Of the three populations surveyed by histopathology, the prevalence of chronic laminitis ranged between 40% and 93%. Foot health appeared to be affected by the environment inhabited by the horses. The observed chronic laminitis may be attributable to either nutritional or traumatic causes. Given the overwhelming evidence of suboptimal foot health, it may not be appropriate for the feral horse foot to be the benchmark model for equine foot health.
Distances travelled by feral horses in ‘outback’ Australia
Publisher: Wiley
Date: 11-2010
DOI: 10.1111/J.2042-3306.2010.00203.X
Abstract: The distance travelled by Australian feral horses in an unrestricted environment has not previously been determined. It is important to investigate horse movement in wilderness environments to establish baseline data against which the movement of domestically managed horses and wild equids can be compared. To determine the travel dynamics of 2 groups of feral horses in unrestricted but different wilderness environments. Twelve feral horses living in 2 wilderness environments (2000 vs. 20,000 km(2)) in outback Australia were tracked for 6.5 consecutive days using custom designed, collar mounted global positioning systems (GPS). Collars were attached after darting and immobilising the horses. The collars were recovered after a minimum of 6.5 days by re-darting the horses. Average daily distance travelled was calculated. Range use and watering patterns of horses were analysed by viewing GPS tracks overlaid on satellite photographs of the study area. Average distance travelled was 15.9 ± 1.9 km/day (range 8.1-28.3 km/day). Horses were recorded up to 55 km from their watering points and some horses walked for 12 h to water from feeding grounds. Mean watering frequency was 2.67 days (range 1-4 days). Central Australian horses watered less frequently and showed a different range use compared to horses from central Queensland. Central Australian horses walked for long distances in direct lines to patchy food sources whereas central Queensland horses were able to graze close to water sources and moved in a more or less circular pattern around the central water source. The distances travelled by feral horses were far greater than those previously observed for managed domestic horses and other species of equid. Feral horses are able to travel long distances and withstand long periods without water, allowing them to survive in semi-arid conditions.
Diagnosis of equine endocrinopathies: The value of measuring blood glucose during an oral glucose test
Publisher: Elsevier BV
Date: 10-2023
Novel keratins identified by quantitative proteomic analysis as the major cytoskeletal proteins of equine (Equus caballus) hoof lamellar tissue1
Publisher: Oxford University Press (OUP)
Date: 12-2010
Abstract: The dermo-epidermal interface that connects the equine distal phalanx to the cornified hoof wall withstands great biomechanical demands, but is also a region where structural failure often ensues as a result of laminitis. The cytoskeleton in this region maintains cell structure and facilitates intercellular adhesion, making it likely to be involved in laminitis pathogenesis, although it is poorly characterized in the equine hoof lamellae. The objective of the present study was to identify and quantify the cytoskeletal proteins present in the epidermal and dermal lamellae of the equine hoof by proteomic techniques. Protein was extracted from the mid-dorsal epidermal and dermal lamellae from the front feet of 5 Standardbred geldings and 1 Thoroughbred stallion. Mass spectrometry-based spectral counting techniques, PAGE, and immunoblotting were used to identify and quantify cytoskeletal proteins, and indirect immunofluorescence was used for cellular localization of K14 and K124 (where K refers to keratin). Proteins identified by spectral counting analysis included 3 actin microfilament proteins 30 keratin proteins along with vimentin, desmin, peripherin, internexin, and 2 lamin intermediate filament proteins and 6 tubulin microtubule proteins. Two novel keratins, K42 and K124, were identified as the most abundant cytoskeletal proteins (22.0 ± 3.2% and 23.3 ± 4.2% of cytoskeletal proteins, respectively) in equine hoof lamellae. Immunoreactivity to K14 was localized to the basal cell layer, and that to K124 was localized to basal and suprabasal cells in the secondary epidermal lamellae. Abundant proteins K124, K42, K14, K5, and α(1)-actin were identified on 1- and 2-dimensional polyacrylamide gels and aligned with the results of previous studies. Results of the present study provide the first comprehensive analysis of cytoskeletal proteins present in the equine lamellae by using mass spectrometry-based techniques for protein quantification and identification.
Advanced glycation endproducts in horses with insulin-induced laminitis
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.VETIMM.2011.12.016
Abstract: Advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of cancer, inflammatory conditions and diabetic complications. An interaction of AGEs with their receptor (RAGE) results in increased release of pro-inflammatory cytokines and reactive oxygen species (ROS), causing damage to susceptible tissues. Laminitis, a debilitating foot condition of horses, occurs in association with endocrine dysfunction and the potential involvement of AGE and RAGE in the pathogenesis of the disease has not been previously investigated. Glucose transport in lamellar tissue is thought to be largely insulin-independent (GLUT-1), which may make the lamellae susceptible to protein glycosylation and oxidative stress during periods of increased glucose metabolism. Archived lamellar tissue from horses with insulin-induced laminitis (n=4), normal control horses (n=4) and horses in the developmental stages (6h, 12h and 24h) of the disease (n=12) was assessed for AGE accumulation and the presence of oxidative protein damage and cellular lipid peroxidation. The equine-specific RAGE gene was identified in lamellar tissue, sequenced and is now available on GenBank. Lamellar glucose transporter (GLUT-1 and GLUT-4) gene expression was assessed quantitatively with qRT-PCR in laminitic and control horses and horses in the mid-developmental time-point (24 h) of the disease. Significant AGE accumulation had occurred by the onset of insulin-induced laminitis (48 h) but not at earlier time-points, or in control horses. Evidence of oxidative stress was not found in any group. The equine-specific RAGE gene was not expressed differently in treated and control animals, nor was the insulin-dependent glucose transporter GLUT-4. However, the glucose transporter GLUT-1 was increased in lamellar tissue in the developmental stages of insulin-induced laminitis compared to control horses and the insulin-independent nature of the lamellae may facilitate AGE formation. However, due to the lack of AGE accumulation during disease development and a failure to detect an increase in ROS or upregulation of RAGE, it appears unlikely that oxidative stress and protein glycosylation play a central role in the pathogenesis of acute, insulin-induced laminitis.
Associations between feeding and glucagon‐like peptide‐2 in healthy ponies
Publisher: Wiley
Date: 13-09-2023
DOI: 10.1111/EVJ.14004
Histopathological examination of chronic laminitis in Kaimanawa feral horses of New Zealand
Publisher: Informa UK Limited
Date: 09-2012
DOI: 10.1080/00480169.2012.682271
Abstract: To investigate the prevalence, histopathological and histomorphometric presentation of chronic laminitis in a population of Kaimanawa feral horses. Following the capture and euthanasia of feral horses from the Kaimanawa Ranges of New Zealand, the left forefoot of 28 stallions and 28 mares aged between 6 and 12 years were removed and processed for histology. Sections of lamellar s les from each horse were examined using light microscopy. The presence of laminitis was assessed and the histopathological lesions were described. Horses were grouped by histological diagnosis into laminitic and non-laminitic groups and histomorphometric analysis was conducted and compared between groups. The parameters examined were total length of primary epidermal lamellae (PEL), keratinised length of PEL, and the length of secondary epidermal lamellae (SEL) at the abaxial end and axial end of each PEL. Of the horses examined, 25 (45%) were diagnosed with chronic laminitis. The most prevalent histopathological features were the presence of excessive cap horn, and multi-branched and attenuated SEL. Histomorphometric assessment of the lamellar architecture revealed no difference in morphometric measurements between the normal and laminitic groups for any parameter measured (p>0.05). The current study found a high prevalence of laminitis in feral Kaimanawa horses. The reason for this in the Kaimanawa population is not known. Histomorphometric analysis may not be a good indicator of chronic laminitis in feral horses. It is an important finding that the feral horse lifestyle in the environment of the Kaimanawa Ranges in New Zealand offers no protection against foot disease. The finding suggests that horses are vulnerable to laminitis whether in domestic care or in a feral habitat.
Phenotypic, hormonal, and clinical characteristics of equine endocrinopathic laminitis
Publisher: Wiley
Date: 29-01-2019
DOI: 10.1111/JVIM.15419
Prolonged hyperinsulinemia affects metabolic signal transduction markers in a tissue specific manner
Publisher: Elsevier BV
Date: 04-2016
DOI: 10.1016/J.DOMANIEND.2015.11.001
Abstract: Insulin dysregulation is common in horses although the mechanisms of metabolic dysfunction are poorly understood. We hypothesized that insulin signaling in striated (cardiac and skeletal) muscle and lamellae may be mediated through different receptors as a result of receptor content, and that transcriptional regulation of downstream signal transduction and glucose transport may also differ between tissues sites during hyperinsulinemia. Archived s les from horses treated with a prolonged insulin infusion or a balanced electrolyte solution were used. All treated horses developed marked hyperinsulinemia and clinical laminitis. Protein expression was compared across tissues for the insulin receptor and insulin-like growth factor 1 receptor (IGF-1R) by immunoblotting. Gene expression of metabolic insulin-signaling markers (insulin receptor substrate 1, Akt2, and glycogen synthase kinase 3 beta [GSK-3β]) and glucose transport (basal glucose transporter 1 and insulin-sensitive glucose transporter 4) was evaluated using real-time reverse transcription polymerase chain reaction. Lamellar tissue contained significantly more IGF-1R protein than skeletal muscle, indicating the potential significance of IGF-1R signaling for this tissue. Gene expression of the selected markers of insulin signaling and glucose transport in skeletal muscle and lamellar tissues was unaffected by prolonged hyperinsulinemia. In contrast, the significant upregulation of Akt2, GSK-3β, GLUT1, and GLUT4 gene expression in cardiac tissue suggested that the prolonged hyperinsulinemia induced an increase in insulin sensitivity and a transcriptional activation of glucose transport. Responses to insulin are tissue-specific, and extrapolation of data across tissue sites is inappropriate.
Glucagon-like peptide-2: A potential role in equine insulin dysregulation.
Publisher: Wiley
Date: 26-03-2018
DOI: 10.1111/EVJ.12825
Abstract: Equine insulin dysregulation (ID) is a common and poorly understood disorder that increases the risk of laminitis. Recent data show that the condition may be associated with alteration of the enteroinsular axis and enhanced glucose bioavailability. Upregulation of glucagon-like peptide-2 (GLP-2), an intestinotrophic peptide, leads to enhanced nutrient uptake and metabolic dysfunction in other species. The study aimed to 1) determine whether GLP-2 is differentially expressed in insulin-dysregulated ponies, compared with healthy ponies, and 2) confirm intestinal expression of the GLP-2 receptor in horses (eGLP-2R). Cohort study. Fasting and post-prandial GLP-2 concentrations were measured in archived plasma s les obtained from 25 mixed-breed ponies during two feeding studies. Measurements were undertaken with an ELISA that was validated for equine use as part of the current study. Ponies were designated as healthy or insulin-dysregulated based on an oral glucose test, and the results were compared between groups. The gene expression of the eGLP-2R was determined with polymerase chain reaction. Basal, fasted plasma GLP-2 concentrations were higher in ponies with ID, compared with healthy ponies. Grazing increased GLP-2 in healthy, but not in insulin-dysregulated, ponies. The eGLP-2R gene was expressed in the small intestine and pancreas. The study was performed with a relatively small s le size. The specificity of the GLP-2 assay could not be determined due to the lack of equine-specific assay standards. This study has demonstrated that GLP-2 may be important in the pathogenesis of equine ID and suggests that the eGLP-2R may be a novel therapeutic target for the treatment of equine ID.
The application of a new laminitis scoring method to model the rate and pattern of improvement from equine endocrinopathic laminitis in a clinical setting
Publisher: Springer Science and Business Media LLC
Date: 07-01-2021
DOI: 10.1186/S12917-020-02715-7
Abstract: Endocrinopathic, or hyperinsulinaemia-associated laminitis (HAL) is a common and debilitating equine foot disease, and although no pharmacological treatments are registered, several are under development. To evaluate the effect of such treatments, an accurate and consistent method is needed to track the clinical signs of laminitis over time, and the natural history of the disease, in terms of a ‘normal’ pattern of improvement, needs to be understood. This study examined the improvement pattern in clinical cases of naturally-occurring HAL subjected to a range of best-practice interventions, using two different scoring methods. Eighty horses and ponies with suspected HAL were enrolled in a study conducted at 16 veterinary practices across Germany. The severity of laminitis was assessed by independent veterinarians using both the traditional Obel method and a modified Obel method developed by Meier and colleagues. Assessments were made on the day of diagnosis (d 0), then on days 4, 9, 14, 25 and 42 during the intervention period. Pain medications were withheld for 24 h prior to clinical examination in all cases. Time to marked improvement from laminitis varied between in iduals, but was difficult to monitor accurately using the Obel method, with the median grade being 2/4 on days 0 and 4, then 0/4 from d 9 onwards. More subtle changes could be identified using the Meier method, however, and the median scores were seen to follow the form of an exponential decay model in most horses, improving from 8/12 on d 0, to 0/12 on d 25. Within this composite scoring method, considerable variation was observed in the rate of improvement of in idual clinical signs, with the average time taken for each sign to reach a median score of 0 ranging from 4 days (foot lift and weight shifting) to 25 days (gait when turned in a circle) across all 80 horses. The Meier method provides a reliable and consistent method for monitoring the clinical status of horses with HAL, and despite the variability, the pattern of improvement described here should provide a useful benchmark against which in idual cases and new treatments can be assessed.
The diagnosis of equine insulin dysregulation
Publisher: Wiley
Date: 23-06-2017
DOI: 10.1111/EVJ.12703
Abstract: Insulin dysregulation is the hallmark of equine metabolic syndrome and has received attention because of its direct association with laminitis. In the absence of an adequate treatment for laminitis, a focus on prophylaxis is needed, making early detection of in iduals at risk of developing laminitis one of the main challenges in equine endocrinology. Recent studies have shown that insulin dysregulation goes beyond tissue insulin resistance and it is now demonstrated that the equine enteroinsular axis plays a major role in insulin secretion and equine hyperinsulinaemia. In this review, we discuss the different tests currently available to diagnose insulin dysregulation in horses: the ones investigating tissue insulin resistance and those investigating the enteroinsular axis, detailing their goals, practicalities and limitations. This review supports the contention that the diagnosis of equine insulin dysregulation should now be based on the investigation of both tissue insulin resistance and the equine enteroinsular axis. Regardless of the tests used many factors of variation, such as breed, diet, fasting state or season, have been identified and could potentially confound the results of a specific test. Therefore, careful interpretation of the results of a given test in each in idual situation is required to optimise the detection of horses at risk of laminitis.
Drug–polymer conjugates with dynamic cloud point temperatures based on poly(2-oxazoline) copolymers
Publisher: Royal Society of Chemistry (RSC)
Date: 2020
DOI: 10.1039/D0PY00602E
Abstract: A shift in cloud point temperatures of poly(2-oxazoline)/ACE inhibitor polymer drug conjugates occurs on release of the drug.
Incidence and risk factors for recurrence of endocrinopathic laminitis in horses
Publisher: Wiley
Date: 10-04-2019
DOI: 10.1111/JVIM.15497
An investigation of the equine epidermal growth factor system during hyperinsulinemic laminitis
Publisher: Public Library of Science (PLoS)
Date: 05-12-2019
Carbohydrate pellets to assess insulin dysregulation in horses
Publisher: Wiley
Date: 30-12-2022
DOI: 10.1111/JVIM.16621
Abstract: A glycemic challenge test is used for the diagnosis of insulin dysregulation (ID) in horses and ponies. Different forms of the test exist where the administrative route and dose of glucose vary, which makes interpretation of results challenging. To evaluate the palatability of, and blood glucose and insulin responses to, carbohydrate pellets fed as an oral glucose test (OGT), and to establish the diagnostic threshold for ID when using the pellets. University and privately‐owned horses and ponies ( n = 157) comprised of 31 breeds and both sexes. Multicenter cohort study. A custom‐produced glycemic pellet was offered for free intake at 0.5 g/kg BW soluble carbohydrate and serum insulin and blood glucose concentrations measured before and after (60, 120, and 180 minutes) the pellets were offered. Pellet acceptance and intake time (those that finished within 10 minutes) were determined to assess palatability. The pellets were palatable to 132/157 animals, and ponies found the pellets more ( P = .004) palatable than horses. The median intake time (4 [3‐6] minutes) was positively correlated with acceptance grade ( r = .51 P .0001). Consumption of the pellets elicited peak blood glucose (6.6 [5.8‐7.8] mmol/L) and serum insulin (40.5 [19‐99.8] μIU/mL) responses at 120 minutes. At 120 minutes the optimal cut‐off was 83 μIU/mL (95% CI: 70‐99 μIU/mL) for the IMMULITE 2000XPi assay. The pellets were palatable and a suitable, novel carbohydrate source for the OGT.
Endocrine and Metabolic Diseases
Publisher: Elsevier
Date: 2020
The effect of diet change and insulin dysregulation on the fecal microbiome of ponies
Publisher: The Company of Biologists
Date: 2020
DOI: 10.1242/JEB.219154
Abstract: The equine microbiome can change in response to dietary alteration and might play a role in insulin dysregulation. The aim of this study was to determine the effect of adding pasture to a hay diet on the fecal bacterial microbiome of both healthy and insulin-dysregulated ponies. Fecal s les were collected from sixteen ponies before and after dietary change to enable bacterial 16S rRNA sequencing of the V3-V4 region. The dominant phyla in all s les were the Firmicutes and Bacteroidetes. The evenness of the bacterial populations decreased after grazing pasture, and when a pony was moderately insulin-dysregulated (P=0.001). Evenness scores negatively correlated with post-prandial glucagon-like peptide-1 concentrations after a hay-only diet (r2 =-0.7, P=0.001). A change in diet explained 3% of fecal microbiome variability. We conclude that metabolically healthy ponies have greater microbial stability when challenged with a subtle dietary change, compared to moderately insulin-dysregulated ponies.
Equine laminitis: Induced by 48 h hyperinsulinaemia in Standardbred horses
Publisher: Wiley
Date: 09-02-2010
Equine pituitary pars intermedia dysfunction: current understanding and recommendations from the Australian and New Zealand Equine Endocrine Group
Publisher: Wiley
Date: 03-06-2018
DOI: 10.1111/AVJ.12716
Abstract: The purpose of this article is to provide a review of the current knowledge and opinions about the epidemiology, clinical findings (including sequelae), diagnosis, treatment and monitoring of equine pituitary pars intermedia dysfunction, particularly in the Australian context. This information and the recommendations provided will assist practitioners in making informed decisions regarding the diagnosis and management of this disorder.
Effects of insulin on IGF-1 receptors in equine lamellar tissue in vitro
Publisher: Elsevier BV
Date: 2021
DOI: 10.1016/J.DOMANIEND.2020.106530
Abstract: Although it is understood that equine endocrinopathic laminitis can be triggered by high concentrations of insulin, it is unclear whether this represents a direct action on lamellar tissue via insulin receptors (InsR), an interaction with IGF-1 receptors (IGF-1R), or some other, indirect action. This uncertainty is because of the reported scarcity of InsR in lamellar tissue and the low affinity of insulin for equine IGF-1R. In the present study, the effects of insulin and IGF-1 (as a positive control) were examined using lamellar explants isolated from the hooves of healthy horses and incubated in cell culture medium for between 2 min and 48 h. In this system, a low physiological concentration of IGF-1 (10 nM 1.31 ng/mL) caused a marked increase in the appearance of phosphorylated IGF-1R after 5 min (P < 0.05), and this effect was blocked by a human anti-IGF-1R monoclonal antibody (mAb). However, a high concentration of insulin (10 nM 1,430 μIU/mL) appeared to cause dephosphorylation of the IGF-1R after 5 min (P < 0.01), 15 min, and 30 min (P < 0.001). Using
The effect of oral and intravenous dextrose on C-peptide secretion in ponies1
Publisher: Oxford University Press (OUP)
Date: 02-2016
Abstract: Managing equine hyperinsulinemia is crucial for preventing laminitis, but our understanding of the mechanisms involved in insulin dysregulation in this species is incomplete. C-peptide is co-secreted with insulin but is resistant to hepatic metabolism and can be used to study insulin dysregulation. This study examined C-peptide secretion in serial blood s les collected after oral and i.v. dextrose (0.75 g/kg) administration to 9 ponies (BCS, 7.1 ± 0.5). The ponies were designated as hyperinsulinemic (HI) or normoinsulinemic (NI) responders before the study, using oral glucose tests and fasted glucose-to-insulin ratios, and responses were compared between the 2 groups. C-peptide concentrations increased ( < 0.01) rapidly from fasted levels after both oral and i.v. dextrose, with similar area under the concentration-time curve (AUC) for both tests and a significant correlation with AUC. The AUC was similar in HI and NI ponies after i.v. dextrose, indicating similar pancreatic capacity for both groups. However, for oral dextrose, the AUC and the AUC were markedly higher ( < 0.05) in the HI ponies, indicating a greater secretion rate of these peptides. Slower insulin clearance might have also contributed to the larger AUC in HI ponies, but this hypothesis requires further investigation with specific measures of hepatic insulin clearance.
Equine glucagon-like peptide-1 receptor physiology
Publisher: PeerJ
Date: 29-01-2018
DOI: 10.7717/PEERJ.4316
Abstract: Equine metabolic syndrome (EMS) is associated with insulin dysregulation, which often manifests as post-prandial hyperinsulinemia. Circulating concentrations of the incretin hormone, glucagon-like peptide-1 (GLP-1) correlate with an increased insulin response to carbohydrate intake in animals with EMS. However, little is known about the equine GLP-1 receptor (eGLP-1R), or whether GLP-1 concentrations can be manipulated. The objectives were to determine (1) the tissue localisation of the eGLP-1R, (2) the GLP-1 secretory capacity of equine intestine in response to glucose and (3) whether GLP-1 stimulated insulin secretion from isolated pancreatic islets can be attenuated. Archived and abattoir-sourced tissues from healthy horses were used. Reverse transcriptase PCR was used to determine the tissue distribution of the eGLP-1R gene, with immunohistochemical confirmation of its pancreatic location. The GLP-1 secretion from intestinal explants in response to 4 and 12 mM glucose was quantified in vitro . Pancreatic islets were freshly isolated to assess the insulin secretory response to GLP-1 agonism and antagonism in vitro , using concentration-response experiments. The eGLP-1R gene is widely distributed in horses (pancreas, heart, liver, kidney, duodenum, digital lamellae, tongue and gluteal skeletal muscle). Within the pancreas the eGLP-1R was immunolocalised to the pancreatic islets. Insulin secretion from pancreatic islets was concentration-dependent with human GLP-1, but not the synthetic analogue exendin-4. The GLP-1R antagonist exendin 9-39 (1 nM) reduced ( P = 0.08) insulin secretion by 27%. The distribution of the eGLP-1R across a range of tissues indicates that it may have functions beyond insulin release. The ability to reduce insulin secretion, and therefore hyperinsulinemia, through eGLP-1R antagonism is a promising and novel approach to managing equine insulin dysregulation.
Toll-like receptor and pro-inflammatory cytokine expression during prolonged hyperinsulinaemia in horses: Implications for laminitis
Publisher: Elsevier BV
Date: 2014
DOI: 10.1016/J.VETIMM.2013.10.010
Abstract: Equine laminitis, a disease of the lamellar structure of the horse's hoof, can be incited by numerous factors that include inflammatory and metabolic aetiologies. However, the role of inflammation in hyperinsulinaemic laminitis has not been adequately defined. Toll-like receptor (TLR) activation results in up-regulation of inflammatory pathways and the release of pro-inflammatory cytokines, including interleukin-6 (IL-6) and tumour necrosis factor-alpha (TNF-α), and may be a pathogenic factor in laminitis. The aim of this study was to determine whether TLR4 expression and subsequent pro-inflammatory cytokine production is increased in lamellae and skeletal muscle during equine hyperinsulinaemia. Standardbred horses were treated with either a prolonged, euglycaemic hyperinsulinaemic cl (p-EHC) or a prolonged, glucose infusion (p-GI), which induced marked and moderate hyperinsulinaemia, respectively. Age-matched control horses were treated simultaneously with a balanced electrolyte solution. Treated horses developed clinical (p-EHC) or subclinical (p-GI) laminitis, whereas controls did not. Skeletal muscle and lamellar protein extracts were analysed by Western blotting for TLR4, IL-6, TNF-α and suppressor of cytokine signalling 3 (SOCS3) expression. Lamellar protein expression of TLR4 and TNF-α, but not IL-6, was increased by the p-EHC, compared to control horses. A significant positive correlation was found between lamellar TLR4 and SOCS3. Skeletal muscle protein expression of TLR4 signalling parameters did not differ between control and p-EHC-treated horses. Similarly, the p-GI did not result in up-regulation of lamellar protein expression of any parameter. The results suggest that insulin-sensitive tissues may not accurately reflect lamellar pathology during hyperinsulinaemia. While TLR4 is present in the lamellae, its activation appears unlikely to contribute significantly to the developmental pathogenesis of hyperinsulinaemic laminitis. However, inflammation may have a role to play in the later stages (e.g., repair or remodelling) of the disease.
Insulin and the insulin-like growth factor system: a novel theory for hyperinsulinemic laminitis pathogenesis
Publisher: Elsevier BV
Date: 10-2011
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