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.
Samimi AS, Samimi K, Karimiafshar M, Tajik J.The objective of this study was to comparatively evaluate the anti-inflammatory effects of intravenous administration of insulin (in different doses) and flunixin on physiological variables, acute-phase responses, and cardiovascular biomarkers during inflammatory phase which was induced by Escherichia coli lipopolysaccharide (LPS) serotype O55:B5 in miniature donkeys. A total of twenty-four clinically healthy male adult miniature donkeys aged 5 ± 1 year and weighing 120 ± 10 kg were studied. The animals were assigned randomly to four experimental groups (three treatment and one positive co...
Loos CMM, Dorsch SC, Elzinga SE, Brewster-Barnes T, Vanzant ES, Adams AA, Urschel KL.Equine metabolic syndrome (EMS) is characterized by an abnormal insulin response to a glycemic challenge but despite the known insulinotropic effects of certain amino acids, there is a paucity of data evaluating the impact of dietary protein on insulin dynamics in these horses. The objective was therefore to assess insulin and amino acid responses following intake of a high protein meal in healthy horses and those with EMS. Six mature horses diagnosed with EMS and six age-matched control horses without EMS were used. Horses were fed 2g/kg body mass (BM) of a high protein pellet (31% crude prot...
Luethy D, Johnson AL, Stefanovski D, Boston RC, Orsini JA.Equine metabolic syndrome (EMS) is prevalent in the equine population, and somatostatin analogs might be useful for diagnosis and/or treatment of EMS in horses. The purpose of this study was to evaluate the glucose and insulin responses to subcutaneous and intravenous administration of somatostatin. Six healthy research horses were included in this prospective study. An initial pilot study was performed to assess several different doses (10-22 µg/kg [4.5-10 µg/lb]) in two horses, then a final dosage of 22 µg/kg (10 µg/lb) was administered to six horses IV and SQ in a two-period random...
Fradinho MJ, Mateus L, Bernardes N, Bessa RJB, Caldeira RM, Ferreira-Dias G.Development of a healthy musculoskeletal system is of high concern for horse breeders and users. A longitudinal field study was performed in order to: (i) evaluate growth patterns and long-term changes on bone quality, bone metabolism, growth factors and metabolic variables in the Lusitano horse; and (ii) retrospectively assess whether these changes were related with radiographic findings regarding osteochondrosis-like lesions (OC) at the onset of training. Thirty-four Lusitano foals born and raised at four stud-farms, were periodically weighed (BW), and measured (withers height-WH) from birth...
Ragno VM, Zello GA, Klein CD, Montgomery JB.Obesity data in people and companion animals are depicting a future of increasing morbidity, cost for society, and significant health and welfare concerns. Between 25 and 50% of cats, dogs, and horses in developed countries are overweight or obese, which mirrors the situation in humans. Equine metabolic syndrome (EMS) was named after human metabolic syndrome (MetS), which has about 30 years of lead in research efforts. Even though the complications of the two syndromes seem to grossly differ (cardiac vs. laminitis risk), a number of similar disease mechanisms are worthy of investigation. Sinc...
Bourebaba L, Bedjou F, Röcken M, Marycz K.Equine metabolic syndrome (EMS) refers to a cluster of associated abnormalities and metabolic disorders, including insulin resistance and adiposity. The numerous biological properties of mesenchymal stem cells (MSCs), including self-renewal and multipotency, have been the subject of many in-depth studies, for the management of EMS; however, it has been shown that this cell type may be affected by the condition, impairing thus seriously their therapeutic potential. Therefore, an attempt to rescue EMS adipose-derived stem cells (ASCs) with calystegines (polyhydroxylated alkaloids) that are endow...
Moser K, Banse H.The objectives of this study were to compare the insulin and glucose responses of horses to 2 formulations of corn syrup, [Karo Light (Karo) available in the United States, and Crown Lily White (Crown), available in Canada]. Horses were evaluated under both fed ( = 14) and fasted ( = 10) conditions. Using a randomized crossover design, each horse underwent an oral sugar test using Karo or Crown syrup. There were no significant differences in insulin or glucose time of maximum concentration (T), maximum concentration (C), or area under the curve (AUC) or in insulin or glucose concentrations at ...
van Eps AW, Burns TA.Laminitis is a consequence of primary disease processes elsewhere in the body. The key pathophysiologic events are insulin dysregulation in endocrinopathic laminitis, ischemia in supporting limb laminitis, and inflammation in sepsis-related laminitis. These apparently disparate mechanisms converge to cause lamellar attachment failure through epithelial cell adhesion loss and stretch, possibly mediated by common growth factor signaling pathways. Tissue damage through mechanical distraction, inflammation, pain, and a proliferative epithelial healing response are features of acute laminitis regar...
Serwotka-Suszczak AM, Marcinkowska KA, Smieszek A, Michalak IM, Grzebyk M, Wiśniewski M, Marycz KM.Insulin resistance (IR) is one of the characteristic features of equine metabolic syndrome (EMS). Presently, the only therapies of choice are caloric restrictions combined with mineral supplementation, which might improve insulin sensitivity. In this study we investigated the effect of Haematococcus pluvialis algae water extract enriched in bioaccumulation process in magnesium ions (Hp_Mg(II)) on equine adipose derived mesenchymal stromal stem cells, in which insulin resistance was induced by palmitic acid (IR-EqASCs). For this purpose, chemical characterization of H. pluvialis was performed w...
Lindåse S, Johansson H, Månsby M, Bröjer J.The hyperglycaemic clamp has been used for measurement of insulin sensitivity (IS) but not for measurement of β-cell response in the horse. However, the repeatability of this test has not been reported for horses. Objective: To determine the repeatability and reliability of measures for IS and β-cell response to glucose using the hyperglycaemic clamp in horses. Methods: Repeated measures, longitudinal study. Methods: Six healthy Standardbred mares underwent a 120-min hyperglycaemic clamp on two occasions with a 10-day washout period. Indices of repeatability and reliability were calculated f...
McFarlane D.Despite there being only 2 common endocrine diseases in horses, pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS), diagnosis is still confusing. Failing to consider horse factors and treating based on laboratory results only have caused many animals to receive lifelong drug treatment unnecessarily. Increased plasma ACTH, baseline or TRH stimulated, supports a diagnosis of PPID; however, breed, age, thriftiness, illness, coat color, geography, diet, and season also affect ACTH concentration. Insulin dysregulation, the hallmark of EMS, can result from insulin resis...
Robles M, Couturier-Tarrade A, Derisoud E, Geeverding A, Dubois C, Dahirel M, Aioun J, Prezelin A, Calvez J, Richard C, Wimel L, Chavatte-Palmer P.Foals born to primiparous mares are lighter and less mature than those born to multiparous dams. Factors driving this difference are not totally understood. Using 7 multiparous and 6 primiparous standardbred mares, we demonstrated that, in late gestation, primiparous mares were less insulin resistant compared to multiparous mares, and that their foals had reduced plasma amino-acid concentrations at birth compared to foals born to multiparous mares. Vascular development, as observed through structure and gene expression, and global DNA methylation were also reduced in primiparous placentas. Ano...
Reynolds A, Keen JA, Fordham T, Morgan RA.Obesity is a common feature of equine metabolic syndrome (EMS). In other species, obese adipose tissue shows pathological features such as adipocyte hypertrophy, fibrosis, inflammation and impaired insulin signalling all of which contribute to whole body insulin dysregulation. Such adipose tissue dysfunction has not been investigated in horses. Objective: To determine if obese horses with EMS have adipose tissue dysfunction characterised by adipocyte hypertrophy, fibrosis, inflammation and altered insulin signalling. Methods: Cross-sectional post-mortem study. Methods: Samples of peri-renal (v...
de Laat MA, Reiche DB, Sillence MN, McGree JM.Endocrinopathic laminitis is common in horses and ponies, but the recurrence rate of the disease is poorly defined. Objective: To determine the incidence of, and risk factors for, the recurrence of endocrinopathic laminitis. Methods: Privately owned horses and ponies with acute laminitis (n = 317, of which 276 cases with endocrinopathic laminitis were followed up to study completion). Methods: This prospective cohort study collected data on veterinary-diagnosed cases of acute laminitis for 2 years. Each case was classified on acceptance to the study as endocrinopathic or non-endocrinopathi...
Nostell K, Lindåse S, Edberg H, Bröjer J.There is little evidence that horses with equine metabolic syndrome (EMS) have higher resting blood pressures than horses with normal insulin sensitivity. However, there are indications that EMS horses have an altered dynamic response to the cardiovascular effects of insulin. Objective: To examine heart rate and the systemic blood pressure response in EMS and control horses during insulin infusion. Methods: Cross-sectional study. Methods: Horses were examined with an oral sugar test (OST) and a euglycaemic hyperinsulinaemic clamp (EHC). Based on the results from the OST, the horses were classi...
Moore JL, Siciliano PD, Pratt-Phillips SE.Weight loss plans in horses typically use dietary restriction, but exercise may have additional benefits. This study aimed to compare the effects of a diet or exercise protocol resulting in comparable caloric restriction in obese horses. Ten obese horses were paired according to sex, age, and breed or breed type. One horse from each pair was randomly assigned to either diet (DIET)-intake restricted to approximately 85% of digestible energy requirements or exercise (EX)-exercised to expend approximately 15% of digestible energy requirements, resulting in 85% of requirements available, for 4 we...
Williams CA, Kenny LB, Burk AO.Rotational grazing is a recommended practice for grazing livestock, but little is known about its benefits with respect to grazing horses. The objective of this study was to investigate the effects of continuous (CON) and rotational (ROT) grazing on forage nutrient composition and whether those concentrations influenced circulating glucose and insulin concentrations in the grazing horse. Twelve mature Standardbred mares were paired by age and weight and randomly assigned to 1 replicate of either a 1.5 ha cool-season grass CON or ROT system for a total of 3 mares in each system. Mares on CON we...
Watts MR, Hegedus OC, Eades SC, Belknap JK, Burns TA.Hyperinsulinemia is associated with equine laminitis, and digital lamellar inflammation in equine metabolic syndrome-associated laminitis (EMSAL) is modest when compared with sepsis-associated laminitis. Objective: To characterize digital lamellar inflammation in horses in a euglycemic-hyperinsulinemic clamp (EHC) model of laminitis. Methods: Sixteen healthy adult Standardbred horses. Methods: Prospective experimental study. Horses underwent EHC or saline infusion (CON) for 48 hours or until the onset of Obel grade 1 laminitis. Horses were euthanized, and digital lamellar tissue was collecte...
Meier A, de Laat M, Reiche D, Fitzgerald D, Sillence M.A previous six-week (wk) study demonstrated the potential of the sodium-glucose linked transport inhibitor velagliflozin as a novel treatment for equine insulin dysregulation. The present study examined the safety and efficacy of velagliflozin over 16 wk. of treatment, and over 4 wk. of withdrawal. Twenty-four insulin dysregulated ponies were selected, based on their hyper-responsiveness to a diet challenge meal containing 3.8 g non-structural carbohydrates (NSC)/kg bodyweight (BW). Ponies with serum insulin > 90 μIU/mL either 2 or 4 h after feeding were enrolled, and randomly allocated...
Pritchard A, Nielsen B, McLean A, Robison C, Yokoyama M, Hengemuehle S, Bailey S, Harris P.Donkeys are often kept, especially in industrialized countries, as companion animals. Donkeys have greater digestive efficiency and tend to expend less energy than horses or ponies, which contributes to obesity in nonworking donkeys. Obesity in all equine species increases risk of chronic health conditions such as laminitis and insulin resistance. Previous studies in horses and ponies have documented obesity's potential effects on glucose-insulin dynamics with lower insulin sensitivity and higher insulin responses to glucose. However, limited studies on obesity and its health impacts in donkey...
Stokes SM, Belknap JK, Engiles JB, Stefanovski D, Bertin FR, Medina-Torres CE, Horn R, van Eps AW.Continuous digital hypothermia can prevent the development and progression of laminitis associated with sepsis but its effects on laminitis due to hyperinsulinaemia are unknown. Objective: To determine the effects of continuous digital hypothermia on laminitis development in the euglycaemic hyperinsulinaemic clamp model. Methods: Randomised, controlled (within subject), blinded, experiment. Methods: Eight clinically normal Standardbred horses underwent laminitis induction using the euglycaemic hyperinsulinaemic clamp model (EHC). At initiation of the EHC, one forelimb was continuously cooled (...
Durham AE, Frank N, McGowan CM, Menzies-Gow NJ, Roelfsema E, Vervuert I, Feige K, Fey K.Equine metabolic syndrome (EMS) is a widely recognized collection of risk factors for endocrinopathic laminitis. The most important of these risk factors is insulin dysregulation (ID). Clinicians and horse owners must recognize the presence of these risk factors so that they can be targeted and controlled to reduce the risk of laminitis attacks. Diagnosis of EMS is based partly on the horse's history and clinical examination findings, and partly on laboratory testing. Several choices of test exist which examine different facets of ID and other related metabolic disturbances. EMS is controlled ...
Berryhill EH, Magdesian KG, Tadros EM, Edman JE.Maintaining serum glucose concentrations is critical in neonatal foals and is often dysregulated in illness; however, few studies have assessed the effects of age, or variation of glucose and insulin, in neonates and their postpartum dams. This study aimed to serially evaluate serum glucose and insulin concentrations and glucose/insulin (G/I) ratios in seven healthy foals and their dams immediately postpartum and at 1-2 and 10-12days of age. The hypotheses were that: (1) there would be wide temporal variation in hourly glucose and insulin measurements among foals; and (2) measured parameters i...
de Laat MA, Sillence MN, Reiche DB.Equine endocrinopathic laminitis is common and can be associated with an underlying endocrinopathy, such as equine metabolic syndrome (EMS), pituitary pars intermedia dysfunction (PPID), pasture consumption, or any combination of these factors. Objective: The aim of the study was to improve the risk assessment capabilities of clinicians, and to inform management strategies, for acute endocrinopathic laminitis by prospectively examining the phenotypic, hormonal, and clinical characteristics of the disease in a large cohort. Methods: Privately owned horses and ponies (n = 301) of any age, se...
Blaue D, Schedlbauer C, Starzonek J, Gittel C, Brehm W, Einspanier A, Vervuert I.The objective of this study was to illuminate the changes in serum NEFA concentrations during a combined glucose-insulin test (CGIT) and basal serum triacylglycerides (TGs) with increasing BW in Shetland ponies and warmblood horses. Therefore, basal blood samples were taken during fasting and a CGIT was performed in 19 healthy equines (10 Shetland ponies, 9 warmblood horses) (t0). After one (t1) and two (t2) year(s) of receiving 200% of their maintenance metabolizable energy requirement, procedures were repeated in the same equines. Sixteen of 19 equines had no signs of insulin dysregulation c...
Norton EM, Avila F, Schultz NE, Mickelson JR, Geor RJ, McCue ME.Ponies are highly susceptible to metabolic derangements including hyperinsulinemia, insulin resistance, and adiposity. Objective: Genetic loci affecting height in ponies have pleiotropic effects on metabolic pathways and increase the susceptibility to equine metabolic syndrome (EMS). Methods: Two hundred ninety-four Welsh ponies and 529 horses. Methods: Retrospective study of horses phenotyped for metabolic traits. Correlations between height and metabolic traits were assessed by Pearson's correlation coefficients. Complementary genome-wide analysis methods were used to identify a region of in...
Cassimeris L, Engiles JB, Galantino-Homer H.Laminitis is often associated with endocrinopathies that cause hyperinsulinemia and is also induced experimentally by hyperinsulinemia, suggesting that insulin initiates laminitis pathogenesis. Hyperinsulinemia is expected to activate pro-growth and anabolic signaling pathways. We hypothesize that chronic over-stimulation of these pathways in lamellar tissue results in endoplasmic reticulum stress, contributing to tissue pathology, as it does in human metabolic diseases. We tested this hypothesis by asking whether lamellar tissue from horses with naturally-occurring endocrinopathic laminitis s...
Norton EM, Schultz NE, Rendahl AK, Mcfarlane D, Geor RJ, Mickelson JR, McCue ME.Equine metabolic syndrome (EMS) is a complex clinical disorder with both environmental and genetic factors contributing to EMS phenotypes. Estimates of heritability determine the proportion of variation in a trait that is attributable to genetics. Objective: To provide heritability estimates for nine metabolic traits associated with EMS in two high-risk breeds. Methods: Retrospective cohort study. Methods: High-density single-nucleotide polymorphism (SNP) genotype data was used to estimate the heritability (h ) of nine metabolic traits relevant to EMS in a cohort of 264 Welsh ponies and 286 M...
Morrison PK, Newbold CJ, Jones E, Worgan HJ, Grove-White DH, Dugdale AH, Barfoot C, Harris PA, Argo CM.Gastrointestinal microbial communities are increasingly being implicated in host susceptibilities to nutritional/metabolic diseases; such conditions are more prevalent in obese and/or older horses. This controlled study evaluated associations between host-phenotype and the fecal microbiome / metabolome. Thirty-five, Welsh Mountain pony mares were studied across 2 years (Controls, = 6/year, 5-15 years, Body Condition Score (BCS) 4.5-6/9; Obese, = 6/year, 5-15 years, BCS > 7/9; Aged, = 6 Year 1; = 5 Year 2, ≥19 years old). Animals were individually fed the same hay to maintenance (2% bo...
Bamford NJ, Potter SJ, Baskerville CL, Harris PA, Bailey SR.The importance of including exercise with dietary modification for the management of obese equids is not clearly understood. Objective: To evaluate the effect of a practical low-intensity exercise regimen, in addition to dietary restriction, on indices of insulin sensitivity (SI) and plasma adipokine concentrations in obese equids. Methods: Twenty-four obese (body condition score [BCS] ≥ 7/9) horses and ponies. Methods: Over a 12-week period, animals received either dietary restriction only (DIET) or dietary restriction plus low-intensity exercise (DIET+EX). All animals were provided wit...
Meier A, de Laat M, Reiche D, Fitzgerald D, Sillence M.A previous six-week (wk) study demonstrated the potential of the sodium-glucose linked transport inhibitor velagliflozin as a novel treatment for equine insulin dysregulation. The present study examined the safety and efficacy of velagliflozin over 16 wk. of treatment, and over 4 wk. of withdrawal. Twenty-four insulin dysregulated ponies were selected, based on their hyper-responsiveness to a diet challenge meal containing 3.8 g non-structural carbohydrates (NSC)/kg bodyweight (BW). Ponies with serum insulin > 90 μIU/mL either 2 or 4 h after feeding were enrolled, and randomly allocated...
Champion ZJ, Vickers MH, Gravance CG, Breier BH, Casey PJ.Growth hormone (GH) and insulin-like growth factor-I (IGF-I) are both present in blood plasma and IGF-I has been measured in epididymal fluid and seminal plasma. This study was designed to investigate the direct effects of GH or IGF-I on the motility of mature equine spermatozoa in vitro. We compared the effects of one concentration (100 ng/ml) of recombinant bovine GH (rbGH) and recombinant human IGF-I (rhIGF-I) on motility and motion characteristics of equine spermatozoa over a 24 h period. Motility was maintained longer in spermatozoa treated with either rbGH or rhIGF-I during a 24 h period...
Stewart AJ.Magnesium (Mg) is an essential macroelement that is required for cellular energy-dependent reactions involving adenosine triphosphate and for the regulation of calcium channel function. Subclinical hypomagnesemia is common in critically ill humans and animals and increases the severity of the systemic inflammatory response syndrome; worsens the systemic response to endotoxins; and can lead to ileus, cardiac arrhythmias, refractory hypokalemia, and hypocalcemia. This article discusses the clinical signs, consequences, and treatment of hypomagnesemia in horses and describes the association of Mg...
Patterson Rosa L, Mallicote MF, Long MT, Brooks SA.An analogous condition to human metabolic syndrome, Equine Metabolic Syndrome (EMS) is defined by several clinical signs including obesity, hyperinsulinemia, and peripheral insulin dysregulation (ID). Affected horses may also exhibit hypertension, hyperlipemia and systemic inflammation. Measures of ID typically comprise the gold-standard for diagnosis in veterinary care. Yet, the dynamic nature of insulin homeostasis and complex procedures of typical assays make accurate quantification of ID and EMS challenging. This work aimed to investigate new strategies for identification of biochemical ma...
de Laat MA, McGowan CM, Sillence MN, Pollitt CC.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 ...
Urschel KL, Escobar J, McCutcheon LJ, Geor RJ.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...
Freestone JF, Wolfsheimer KJ, Kamerling SG, Church G, Hamra J, Bagwell C.Nine Thoroughbred horses were assessed to determine the normal response of insulin, glucose, cortisol, plasma potassium (K) and erythrocyte K through conditioning and to exercise over 400 and 1,000 m. In addition, adrenaline, noradrenaline, cortisol, plasma K, erythrocyte K and L-lactate concentrations were evaluated in response to maximal exercise with and without the administration of acepromazine. Conditioning caused no obvious trends in plasma K, erythrocyte K, insulin or glucose concentration. Serum cortisol increased (P less than 0.05) from the initial sample at Week 1 to Weeks 4 and 5 (...
Frank N, Sommardahl CS, Eiler H, Webb LL, Denhart JW, Boston RC.To evaluate glucose and lipid metabolism in healthy adult horses administered levothyroxine sodium (L-T4). Methods: 12 healthy adult mares. Methods: 8 horses received an incrementally increasing dosage of L-T4 (24, 48, 72, or 96 mg of L-T4/d) for weeks 1 to 8. Each dose was provide between 7 AM and 8 AM in the morning grain meal for 2 weeks. Four additional horses remained untreated. Serum concentrations of nonesterified fatty acids, triglyceride (TG), total cholesterol (TC), and very-low-density lipoprotein (VLDL) were measured and composition of VLDL examined in samples obtained between 8 AM...
Williams CA, Kenny LB, Burk AO.Rotational grazing is a recommended practice for grazing livestock, but little is known about its benefits with respect to grazing horses. The objective of this study was to investigate the effects of continuous (CON) and rotational (ROT) grazing on forage nutrient composition and whether those concentrations influenced circulating glucose and insulin concentrations in the grazing horse. Twelve mature Standardbred mares were paired by age and weight and randomly assigned to 1 replicate of either a 1.5 ha cool-season grass CON or ROT system for a total of 3 mares in each system. Mares on CON we...
Van Den Wollenberg L, Vandendriessche V, van Maanen K, Counotte GHM.Straightforward testing procedures to enable the diagnosis of insulin dysregulation (ID) in horses that are suitable for use in daily veterinary practice are needed because of the risk that ID could result in laminitis. In our study (that included 90 horses), we compared the proportion of horses classified as ID-positive, ID-suspect, and ID-not diagnosed according to the basal insulin concentration (BIC) with the proportion of horses classified as ID-positive or ID-negative according to a practical and feasible version of an oral sugar test (OST). Furthermore, BIC, basal glucose concentration,...
Wearn JG, Suagee JK, Crisman MV, Corl BA, Hulver MW, Hodgson DR, Geor RJ, McCutcheon LJ.Equine metabolic syndrome (EMS) is a condition of obese horses characterized by insulin resistance, systemic inflammation, and an increased risk of laminitis. The pathogenesis of EMS is thought, in part, to be due to inflammatory proteins produced by adipose tissue. Reducing inflammation may decrease the incidence of laminitis in horses with EMS. Pioglitazone hydrochloride, a thiazolidinedione, has efficacy to reduce obesity associated inflammation in humans. Eight normal, adult, horses were administered 1mg/kg pioglitazone for 14 days, and eight horses served as controls. Physical examination...
de Laat MA, Clement CK, Sillence MN, McGowan CM, Pollitt CC, Lacombe VA.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. Objective: We hypothesised that prolonged hyperinsulinaemia alters the regulation of glucose transport in insulin-sensitive tissue and digital lamellae. Our obje...
Karikoski NP, Box JR, Mykkänen AK, Kotiranta VV, Raekallio MR.The oral sugar test (OST) is commonly used to diagnose insulin dysregulation (ID) and equine metabolic syndrome; however, possible seasonal changes in OST results have not been evaluated. Objective: To determine the possible variation in insulin response to OST throughout the year and risk factors associated with maximum insulin concentration (InsMax) and ID. Methods: Prospective, longitudinal cohort study. Methods: The OST was performed on 29 Finnhorses every other month six times. Serum total adiponectin concentration and phenotypic variables related to obesity were also measured. Changes in...
Annandale EJ, Valberg SJ, Mickelson JR, Seaquist ER.Equine polysaccharide storage myopathy (PSSM) is an inherited disorder characterized by the accumulation of glycogen and abnormal polysaccharide in muscle with normal glyco(geno)lytic enzyme activities. The purpose of this study was to evaluate in vivo insulin sensitivity and glucose excursion in PSSM using a euglycemic hyperinsulinemic clamp. In addition, the content of muscle glucose transporters (GLUT1 and GLUT4) and the insulin receptor was determined in muscle biopsies using Western blot analysis. The glycogen content was 1.8-fold higher, and isolated polysaccharide analyzed by iodine abs...
Baskerville CL, Chockalingham S, Harris PA, Bailey SR.In horses and ponies, insulin dysregulation leading to hyperinsulinemia may be associated with increased risk of laminitis, and prolonged infusion of insulin can induce the condition. It is unclear whether insulin may have a direct or indirect effect on the lamellar tissues. Insulin is structurally related to insulin-like growth factor (IGF-1), and can bind the IGF-1 receptor, albeit at a lower affinity than IGF-1. Methods: Immunohistochemistry was performed on formalin-fixed lamellar tissue sections from six normal horses, euthanised for non-research purposes, using an anti-IGF-1 receptor ant...
Beythien E, Wulf M, Ille N, Aurich J, Aurich C.In pregnant mares, peripheral insulin antagonism channels glucose preferentially to the foetus. On the other hand, horses reduce their metabolic activity in winter. Taking these aspects of equine pregnancy and metabolism together, we hypothesized that glucose clearance from blood and the insulin response to glucose do not only change throughout gestation but also with season. To test this hypothesis, the glucose and insulin response to an oral glucose test and relative insulin release were analysed in pregnant mares (n=12) and in geldings (n=10) as controls. Animals were tested in June, Septem...
Heliczer N, Gerber V, Bruckmaier R, van der Kolk JH, de Solis CN.OBJECTIVE To determine whether hypertension, high sympathetic tone, resting and exercising arrhythmias, and echocardiographic changes consistent with hypertensive cardiomyopathy were associated with equine metabolic syndrome (EMS) in ponies. DESIGN Prospective case-control study. ANIMALS 19 privately owned ponies with a diagnosis of EMS (history of laminitis, body condition score ≥ 7/9, cresty neck score ≥ 3/5, and abnormal oral sugar test result; cases) and 20 healthy control ponies. PROCEDURES Heart rate (HR), noninvasively measured arterial blood pressure (BP), markers of autonomic tone...
The Journal of nutritionJune 15, 2006
Volume 136, Issue 7 Suppl 2114S-2121S doi: 10.1093/jn/136.7.2114S
Harris P, Bailey SR, Elliott J, Longland A.Laminitis occurs throughout the world in horses and ponies and has major welfare implications. It is obviously important to be able to recognize and treat the condition in its early stages so that pain and suffering are kept to a minimum. However, ideally it would be preferred to be able to recommend certain interventions/countermeasures that avoid or prevent the condition from occurring in the first place. Because pasture-associated laminitis occurs with grass consumption, one obvious way to avoid the condition is to prevent access to pasture and to feed forage alternatives that are known to ...
Rings LM, Swink JM, Dunbar LK, Burns TA, Toribio RE.The enteroinsular axis (EIA) comprises intestinal factors (incretins) that stimulate insulin release after PO ingestion of nutrients. Glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) are the main incretins. The EIA has not been investigated in healthy neonatal foals but should be important because energy demands are high in healthy foals and dysregulation is frequent in sick foals. Objective: To evaluate the EIA response to carbohydrates or fasting in newborn foals. We hypothesized that incretin secretion would be higher after PO versus IV carbohydrate adm...
Kellon EM, Gustafson KM.Hyperinsulinemia associated with pituitary pars intermedia dysfunction (PPID) and/or equine metabolic syndrome is well documented to put horses at high risk of laminitis. While dietary control of simple sugars and starch is the most effective therapy to control hyperinsulinemia, some horses fail to respond. Ten horses with hyperinsulinemia refractory to diet control, metformin, levothyroxine, and pergolide (if diagnosed with PPID) were treated with sodium-glucose cotransporter-2 inhibitor canagliflozin (Invokana®). Nine horses were hyperglycemic (>5.5 mmol/l) or had a history of hyperglycemia...
Olley RB, Carslake HB, Ireland JL, McGowan CM.Fasting horses for measurement of basal serum insulin concentration (fasting insulin; FI) has been recommended to standardise testing for insulin dysregulation (ID), yet limited data exist comparing it to dynamic tests. This study aimed to compare FI with the combined glucose-insulin test (CGIT) in horses suspect for ID. We hypothesised that FI would have poor sensitivity for detecting ID compared to CGIT using conventional cut-offs. Records were retrieved from CGITs performed in horses fasted for approximately 8h. Serum insulin and glucose concentrations were measured before and for 150min fo...
Suagee JK, Corl BA, Hulver MW, McCutcheon LJ, Geor RJ.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...
Rose RJ, Hodgson DR, Sampson D, Chan W.Plasma biochemical values were measured in 14 horses, before a 160 km endurance ride, immediately after 85 km, immediately after 160 km, after 30 min recovery period and the day after the ride. For statistical analysis, a group of 7 horses that completed the ride at a mean speed of 234 metres per min (m/min) (Fast Group) was compared with 7 horses that completed the ride at a mean speed of 144 m/min (Slow Group). Estimations were made of sodium, potassium, chloride, bicarbonate, glucose, creatinine, urea, bilirubin, iron, total protein, albumin, calcium, phosphate, cholesterol, alkaline phosph...
Kheder MH, Bailey SR, Dudley KJ, Sillence MN, de Laat MA.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 s...
Brøkner C, Austbø D, Næsset JA, Blache D, Bach Knudsen KE, Tauson AH.The hypothesis for this study was that a higher dietary proportion of soluble fibre would result in stable and constant plasma metabolite and regulatory hormone concentrations. The study was a 4×4 Latin Square design with a sequence of 17 days adaptation to the ration followed by 8 sampling days. The feed rations consisted of only timothy hay (H), hay plus molassed sugar beet pulp combined with either whole oats (OB) or barley (BB) and hay plus a loose chaff-based concentrate (M). Four horses were fitted with permanent caecal cannulas and liquid caecal content was withdrawn manually and blood...
Sessions DR, Reedy SE, Vick MM, Murphy BA, Fitzgerald BP.Peripheral insulin resistance is the failure of proper cellular glucose uptake in response to insulin. Insulin resistance and hyperinsulinemia are associated with several disease states in the horse and reproductive function disturbances in humans, including polycystic ovarian syndrome. To test the hypothesis that insulin resistance (IR) and hyperinsulinemia disrupt the estrous cycle in mares, two experiments were conducted to first develop a model to induce IR and to then examine the effect of this model on the duration of the estrous cycle. In Exp. 1, a hyperinsulinemic-euglycemic clamp (HEC...
Stull CL, Rodiek AV.Two experiments were conducted to determine the response of blood glucose, insulin and cortisol levels to four common equine diets. Experiment 1 was designed to determine the diurnal variation of glucose and two glucoregulatory hormones, insulin and cortisol, in four fasting geldings. No diurnal variation was observed in either glucose or insulin levels during the 24-h sampling period. However, cortisol levels did exhibit a circadian rhythm, with elevated values observed in the morning and low values in the evening. Experiment 2 investigated the response of glucose, insulin, cortisol and selec...
Henson FM, Davenport C, Butler L, Moran I, Shingleton WD, Jeffcott LB, Schofield PN.The effects of insulin and insulin-like growth factors (IGFs) I and II on fetal and foal chondrocytes were investigated in vitro. Chondrocytes from the lateral trochlear ridge of the distal femur were obtained from 2 fetuses (280 and 320 days gestation) and one 4-day-old foal and cultured. Membrane proteins consistent with type 1 and type 2 IGF receptors were demonstrated by radioligand cross linking and equilibrium binding analysis. It was demonstrated that both IGF-I and IGF-II acted as mitogens for isolated equine chondrocytes when present as the sole mitogenic factor in monolayer culture. ...
Gordon ME, McKeever KH, Betros CL, Manso Filho HC.Concentrations of hormones related to energy homeostasis may differ between populations with varied body compositions, acting as signals to increase or decrease energy intake and/or expenditure. How these parameters correlate with body composition in horses and how they vary in fit (F) versus unfit (UF) Standardbred racehorses is unclear. The purpose of this study was to test the hypothesis that plasma concentrations of glucose (GLU), insulin (INS), cortisol (CORT), ghrelin (GHRL), adiponectin (ADIP) and leptin (LEP) would be correlated with body composition and differ in fit (F) versus unfit ...
