Topic:Insulin
Insulin is a hormone produced by the pancreas that plays a pivotal role in regulating glucose metabolism in horses. It facilitates the uptake of glucose by cells, thus maintaining blood sugar levels within a normal range. Insulin's function is integral to energy balance and metabolic processes in equines. Disruptions in insulin regulation can lead to metabolic disorders such as Equine Metabolic Syndrome (EMS), characterized by insulin resistance and associated with obesity and laminitis. This page aggregates peer-reviewed research studies and scholarly articles that explore the physiological role, regulatory mechanisms, and clinical implications of insulin in equine health and disease management.
Naturally occurring compensated insulin resistance selectively alters glucose transporters in visceral and subcutaneous adipose tissues without change in AS160 activation. Although the importance of adipose tissue (AT) glucose transport in regulating whole-body insulin sensitivity is becoming increasingly evident and insulin resistance (IR) has been widely recognized, the underlying mechanisms of IR are still not well understood. The purpose of the present study was to determine the early pathological changes in glucose transport by characterizing the alterations in glucose transporters (GLUT) in multiple visceral and subcutaneous adipose depots in a large animal model of naturally occurring compensated IR. AT biopsies were collected from horses, which were clas...
Effects of the insulin-sensitizing drug pioglitazone and lipopolysaccharide administration on insulin sensitivity in horses. Obesity and insulin resistance increase the risk of laminitis in horses. Pioglitazone (PG) is an insulin-sensitizing drug used in humans that is absorbed after oral administration to horses. Objective: PG treatment will increase insulin sensitivity and transcript abundance of glucose and lipid transporters in adipose and skeletal muscle tissues. Methods: Sixteen lean, healthy horses. Methods: Eight horses were administered PG (1 mg/kg bodyweight PO) for 12 days before induction of insulin resistance through IV administration of lipopolysaccharide (LPS). Treated and untreated controls (CN; n = ...
Insulin resistance selectively alters cell-surface glucose transporters but not their total protein expression in equine skeletal muscle. Insulin resistance (IR) has been widely recognized in humans, and more recently in horses, but its underlying mechanisms are still not well understood. The translocation of glucose transporter 4 (GLUT4) to the cell surface is the limiting step for glucose uptake in insulin-sensitive tissues. Although the downstream signaling pathways regulating GLUT translocation are not well defined, AS160 recently has emerged as a potential key component. In addition, the role of GLUT12, one of the most recently identified insulin-sensitive GLUTs, during IR is unknown. Objective: We hypothesized that cell-su...
Successful treatment of hyperkalaemic periodic paralysis in a horse during isoflurane anaesthesia. A 3-year-old, 400 kg, gelding Quarter Horse was presented for investigation of epistaxis. Methods: The horse was bright, alert and responsive with rectal temperature, heart rate and respiration rate within normal limits. Results: During a second general anaesthetic for surgical treatment of guttural pouch mycosis by balloon-tipped catheter occlusion of the right major palatine artery and ligation of the right external carotid artery, signs consistent with hyperkalaemic periodic paralysis (HYPP) were exhibited. These included concurrent hyperkalaemia, hypercapnoea, sinus tachycardia, and muscle...
Effect of feeding a high-protein diet following an 18-hour period of feed withholding on mammalian target of rapamycin-dependent signaling in skeletal muscle of mature horses. To determine the effect of refeeding following an 18-hour period of feed withholding on the phosphorylation of translation initiation factors in the skeletal muscle of mature horses. Methods: 8 adult horses. Methods: Following an 18-hour period of feed withholding, horses either continued to have feed withheld (postabsorptive state) or were fed 2 g/kg of a high-protein feed (33% crude protein) at time 0 and 30 minutes (postprandial state). Blood samples were taken throughout the experimental period. At 90 minutes, a biopsy specimen was taken from the middle gluteal muscle to measure the phosph...
The developmental and acute phases of insulin-induced laminitis involve minimal metalloproteinase activity. 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 expressi...
Doping control analysis of insulin and its analogues in equine urine by liquid chromatography-tandem mass spectrometry. Insulin and its analogues have been banned in both human and equine sports owing to their potential for misuse. Insulin administration can increase muscle glycogen by utilising hyperinsulinaemic clamps prior to sports events or during the recovery phases, and increase muscle size by its chalonic action to inhibit protein breakdown. In order to control insulin abuse in equine sports, a method to effectively detect the use of insulins in horses is required. Besides the readily available human insulin and its synthetic analogues, structurally similar insulins from other species can also be used a...
Glycaemic and insulinaemic responses to feeding hay with different non-structural carbohydrate content in control and polysaccharide storage myopathy-affected horses. The aim of this study was to determine whether the glycaemic/insulinaemic responses to hay with non-structural carbohydrate (NSC, soluble carbohydrate) of 17% (HC), 10% (MC) or 4% (LC) differs in control horses and whether these responses differ between control and horses with polysaccharide storage myopathy (PSSM). Five clinically normal control horses and seven PSSM horses, all unfit and of Quarter Horse breeding (age 9.4 ± 3.4 years, body condition score range: 4.5-6). A crossover design compared the HC and LC hay, with horses randomly assigned to hay type for 5 days, and all horses fed th...
Effects of hyperinsulinemia on glucose and lipid transporter expression in insulin-sensitive horses. Plasma insulin concentrations are elevated (hyperinsulinemia) in horses with obesity-associated insulin resistance. In other species, insulin resistance is partly due to reduced levels of insulin receptor and the insulin-sensitive glucose transporter, and, in vitro, chronic hyperinsulinemic conditions reduce the expression of these proteins. Consumption of grain-based concentrate feeds results in postprandial hyperinsulinemia in horses, and adaptation to these diets is associated with insulin resistance. As such, it is possible that the repeated, chronic postprandial hyperinsulinemia associate...
Clinical assessment of blood glucose homeostasis in horses: comparison of a continuous glucose monitoring system with a combined intravenous glucose and insulin test protocol. The combined glucose-insulin test (CGIT) is helpful for evaluating insulin sensitivity. A continuous glucose monitoring system (CGMS) reports changes in interstitial glucose concentrations as they occur in the blood. Use of the CGMS minimizes animal contact and may be useful when performing a CGIT. Objective: Results obtained using a CGMS are useful for the evaluation of glucose responses during the evaluation of insulin sensitivity in equids. Methods: Seven mature, obese ponies. Methods: Ponies were equipped with CGMS for determination of interstitial glucose concentrations. Glucose (150 mg/k...
Insulin, glucagon, and leptin in critically ill foals. Endocrine dysregulation of hormones of energy metabolism is well documented in critically ill humans, but limited information exists in septic foals. The purpose of this study was to provide information on the hormonal response to energy metabolism in critically ill foals, focusing on insulin, glucagon, and leptin. Objective: Concentrations of insulin, glucagon, leptin, and triglycerides will be higher, whereas glucose concentration will be lower in septic foals than in healthy and sick nonseptic foals. The magnitude of these differences will be associated with severity of disease and nonsurvi...
Histopathology of insulin-induced laminitis in ponies. Ponies with laminitis associated with insulin resistance and hyperinsulinaemia lack systemic and/or intestinal inflammatory signs, suggesting a different pathogenesis potentially reflected in differing histopathology. Objective: To describe the histological appearance and quantify morphological changes in primary and secondary epidermal lamellae (PEL and SEL) of laminitis lesions from ponies with insulin-induced laminitis. Methods: Equine hoof lamellar tissue was obtained from 4 control ponies and 5 ponies with laminitis induced following infusion of insulin (1036 ± 55 µU/ml) while maintai...
Transient diabetes mellitus in a neonatal Thoroughbred foal. To describe the clinical presentation, treatment, and outcome of a neonatal foal diagnosed with transient Type 1 diabetes mellitus. Methods: A 3-day-old Thoroughbred foal presented with a 24-hour history of diarrhea and depression. Coronavirus particles were observed in the feces via electron microscopy. During hospitalization the foal developed hyperglycemia concomitantly with low insulin concentration and an adequate response to exogenous insulin therapy supported a diagnosis of Type 1 diabetes mellitus. The foal required SC insulin for 26 days, but developed complications associated with in...
Pharmacokinetics of metformin after enteral administration in insulin-resistant ponies. To determine pharmacokinetics and plasma steady-state kinetics of metformin after oral or nasogastric administration in insulin-resistant (IR) ponies. Methods: 8 IR ponies. Methods: Metformin (30 mg/kg) was administered to 8 ponies via nasogastric tube Blood samples were collected at intervals for 24 hours. Plasma concentrations of metformin were measured via liquid chromatography-electrospray tandem mass spectroscopy Pharmacokinetic variables were determined via noncompartmental analysis. Metformin (15 mg/kg, PO, twice daily [8 am and 5 pm]) was administered to 4 ponies for an additional 20 d...
Effects of a supplement containing chromium and magnesium on morphometric measurements, resting glucose, insulin concentrations and insulin sensitivity in laminitic obese horses. Obesity and insulin resistance are risk factors for laminitis in equids and supplements containing chromium and magnesium might improve insulin sensitivity. Objective: A supplement containing chromium, magnesium and other nutraceuticals would alter morphometric measurements, blood variables, and insulin sensitivity in laminitic obese horses. Methods: Twelve previously laminitic obese (body condition score ≥ 7/9) horses were randomly allocated to treatment (n = 6) and control (n = 6) groups and 2 obese horses with clinical laminitis were included in the treatment group. Treated animals receiv...
Dietary supplementation with short-chain fructo-oligosaccharides improves insulin sensitivity in obese horses. Obesity and insulin resistance are risk factors for laminitis in horses and ponies, and diet can play an important role in modulating these risk factors. Dietary supplementation with prebiotic fibers, such as short-chain fructo-oligosaccharides (scFOS), has resulted in improvement of insulin sensitivity in obese dogs and rodents. Thus, we hypothesized that scFOS may reduce insulin resistance in obese horses and designed a study to evaluate the effect of dietary supplementation with scFOS on insulin sensitivity. Eight mature Arabian geldings (BW = 523.0 ± 56.5 kg) with an average BCS of 8 were...
Field treatment and management of endocrinopathic laminitis in horses and ponies. Endocrinopathic laminitis in horses and ponies has the potential to cause extensive damage to the feet before clinical signs of laminitis are apparent. Early diagnosis and intervention based on the detection and control of hyperinsulinemia are critical if the crippling changes that are seen in the disease are to be avoided. Preventing endocrinopathic laminitis, rather than treating it, is good practice management benefiting not only equine patients but also their owners.
Association of season and pasture grazing with blood hormone and metabolite concentrations in horses with presumed pituitary pars intermedia dysfunction. Pituitary pars intermedia dysfunction (PPID) is a risk factor for pasture-associated laminitis, which follows a seasonal pattern. Objective: Hormonal responses to season differ between PPID and unaffected horses. Methods: Seventeen horses aged 8-30 years (14 horses ≥ 20 years of age). Methods: Longitudinal observational study. Blood was collected monthly from August 2007 until July 2008 after pasture grazing and again after overnight stall confinement. Blood hormone and metabolite concentrations were measured and pasture grass samples were analyzed to determine carbohydrate content. Analysis...
Proinflammatory cytokine and chemokine gene expression profiles in subcutaneous and visceral adipose tissue depots of insulin-resistant and insulin-sensitive light breed horses. Insulin resistance has been associated with risk of laminitis in horses. Genes coding for proinflammatory cytokines and chemokines are expressed more in visceral adipose tissue than in subcutaneous adipose tissue of insulin-resistant (IR) humans and rodents. Objective: To investigate adipose depot-specific cytokine and chemokine gene expression in horses and its relationship to insulin sensitivity (SI). Methods: Eleven light breed mares. Methods: Animals were classified as IR (SI=0.58+/-0.31x10(-4) L/min/mU; n=5) or insulin sensitive (IS; SI=2.59+/-1.21x10(-4) L/min/mU; n=6) based on results o...
Effects of athletic conditioning on horses with degenerative suspensory ligament desmitis: a preliminary report. Equine degenerative suspensory ligament desmitis (DSLD) is a debilitating condition that has limited response to rest and stall confinement. This study was designed to test the hypothesis that mild to moderate DSLD is not worsened by consistent exercise. Paso Fino and Peruvian Paso horses (two normal horses and four horses with DSLD) were exercised for 30 min every other day for 8 weeks and then pasture rested for 4 months. Gait analysis, radiographs, ultrasound and serum insulin and glucose concentrations were performed prior to the exercise trial and at each time point. Vertical impulse incr...
Serum thyroid hormone, insulin, glucose, triglycerides and protein concentrations in normal horses: association with topical dexamethasone usage. The aim of this study was to determine if topical application of dexamethasone affected the serum concentrations of thyroid hormones (triiodothyronine T(3) and thyroxine T(4)), glucose, triglycerides, total protein and insulin in normal horses. Ten horses were treated twice daily for 10 days with 50 g dexamethasone using an ointment formulation. Thyroid hormones and insulin were assayed using standard radioimmunoassay methods, while glucose, triglycerides and total protein were determined using a standard enzymatic method and the Biuret reaction, respectively. An increase in serum glucose and ...
Localization of insulin-like growth factor-I (IGF-I) and IGF-I receptor (IGF-IR) in equine testes. The insulin-like growth factor-I (IGF-I) is a key regulator of reproductive functions. IGF-I actions are primarily mediated by IGF-IR. The main objective of this research was to evaluate the presence of IGF-I and IGF-I Receptor (IGF-IR) in stallion testicular tissue. The hypotheses of this study were (i) IGF-I and IGF-IR are present in stallion testicular cells including Leydig, Sertoli, and developing germ cells, and (ii) the immunolabelling of IGF-I and IGF-IR varies with age. Testicular tissues from groups of 4 stallions in different developmental ages were used. Rabbit anti-human polyclona...
Endocrinopathic laminitis: reducing the risk through diet and exercise. Certain individual animals appear predisposed to recurrent pasture-associated laminitis, but the exact mechanisms underlying their predisposition remain a fundamental question in laminitis research. The risk of endocrinopathic laminitis can be reduced if steps are taken to improve insulin sensitivity and reduce inflammation using strategies based on exercise and diet. Exercise has been shown to reduce insulin resistance and suppress inflammation, and dietary manipulation can significantly affect insulin sensitivity.
Laminitis and the equine metabolic syndrome. Although much has been written about laminitis in the context of its association with inflammatory processes, recognition is growing that most cases of laminitis examined by veterinarians in private practice are those associated with pasture grazing, obesity, and insulin resistance (IR). The term 'endocrinopathic laminitis' has been adopted to classify the instances of laminitis in which the origin seems to be more strongly associated with an underlying endocrinopathy, such as either IR or the influence of corticosteroids. Results of a recent study suggest that obesity and IR represent the mos...
Hyperinsulinemic laminitis. 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 ...
Hyperleptinemia in mares and geldings: assessment of insulin sensitivity from glucose responses to insulin injection. Four experiments were conducted 1) to assess the use of glucose responses to insulin injections as a means of estimating insulin sensitivity in horses and 2) to compare the insulin sensitivities of normal horses vs. those displaying hyperleptinemia (HL). In Exp. 1, HL mares and geldings (n = 4 each) and 4 mares and geldings with normal leptin concentrations (NL) were injected intravenously with 20 and 100 mU/kg of BW of bovine insulin on 2 separate occasions in December 2008. In Exp. 2, the experimental protocol was repeated in late April 2009. In Exp. 1, the 20 mU/kg of BW dose of insulin cau...
Optimisation of the frequently sampled intravenous glucose tolerance test to reduce urinary glucose spilling in horses. The frequently sampled i.v. glucose tolerance test (FSIGTT) is used to evaluate glucose and insulin dynamics in horses, but it has not been determined whether urinary glucose spilling (UGS) affects results. Objective: UGS occurs in horses during the FSIGTT and this problem can be minimised by adjusting the dextrose and insulin dosages used. Methods: Six mature mares were included in this study. In the first phase, 6 FSIGTT procedures were performed in each horse to evaluate 6 different dextrose dosages. Six different insulin dosages were evaluated during the second phase of the study after adm...
Effects of endotoxaemia and carbohydrate overload on glucose and insulin dynamics and the development of laminitis in horses. Insulin resistance (IR) is a risk factor for pasture-associated laminitis in equids and alimentary carbohydrate overload may trigger laminitis. Whether glucose metabolism responses to carbohydrate overload are more pronounced in insulin-resistant horses requires further study. Objective: Horses pretreated with endotoxin to alter insulin sensitivity differ significantly in their glucose and insulin responses to carbohydrate overload. Methods: Horses (n=24) were divided into 3 groups. A lipopolysaccharide (LPS; n=8) group that received endotoxin as an 8 h 7.5 ng/kg bwt/h i.v. continuous rate inf...
Type 2 diabetes mellitus with pancreatic beta cell dysfunction in 3 horses confirmed with minimal model analysis. Type 2 diabetes mellitus (T2DM) is diagnosed rarely in equine practice although it may be under-recognised. A greater awareness of the condition and therapeutic considerations would be to the benefit of such cases presenting in practice. More investigation into the pharmacological management of these cases is needed. Objective: Three cases of diabetes mellitus were investigated using a specific test for insulin sensitivity and pancreatic beta cell function in order to define accurately and characterise the existence of T2DM in all 3 subjects. Methods: The insulin-modified frequently sampled i....
Seasonal variation in serum concentrations of selected metabolic hormones in horses. Determination of adrenocorticotropic hormone (ACTH) concentration is a commonly used test in the evaluation of endocrine causes of equine laminitis, but the concentration in healthy horses can be high at certain times of year, which alters the specificity of the ACTH test. Objective: To determine if circulating concentrations of ACTH, cortisol, glucose, insulin, and thyroxine vary month to month in healthy horses and in horses with equine metabolic syndrome (EMS). Methods: Nine healthy adult horses were studied on their farm/stable over the course of 1 year. After the diagnosis of EMS, 10 lami...