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.
Berryhill EH, Urbina NS, Marton S, Vernau W, Alonso FH.The Wellness Ready Test (WRT) is a lateral flow, stall-side assay that measures equine insulin in whole blood and requires validation before recommending clinical use. We evaluated intra- and inter-assay precision and linearity and compared the WRT with a radioimmunoassay (RIA). Tested concentrations ranged from 695 pmol/L (100 μIU/mL). For 20 replicates at each insulin level, intra-assay CVs of the WRT for insulin were 13.3%, 12.9%, and 15.3% at low (139-278 pmol/L; 20-40 μIU/mL), intermediate (278-417 pmol/L; 40-60 μIU/mL), and high (>417 >60 μIU/mL) concentrations...
Kirkwood NC, Hughes KJ, Stewart AJ.Substantial morbidity results from pituitary pars intermedia dysfunction (PPID) which is often underestimated by owners and veterinarians. Clinical signs, pathophysiology, diagnostic tests, and treatment protocols of this condition are reviewed. The importance of improved recognition of early clinical signs and diagnosis are highlighted, as initiation of treatment will result in improved quality of life. Future research should be targeted at improving the accuracy of the diagnosis of PPID, as basal adrenocorticotropic hormone (ACTH) concentration can lack sensitivity and thyrotropin releasing ...
Jayathilake WMNK, Furr M, Risco C, Lacombe VA.Similar to human diabetes, equine metabolic syndrome (EMS) causes insulin dysregulation leading to debilitating sequela including laminitis. The pathophysiological mechanisms underlying EMS and laminitis are not well known. Therefore, using an insulin-resistant equine model, we hypothesized that insulin dysregulation induces an increased expression of inflammatory proteins in a tissue specific manner. Two groups of horses (n = -5/group) were categorized as insulin-resistant (IR) or insulin-sensitive (IS), using a frequently sampled intra-venous glucose tolerance test. Biopsies from skeletal ...
Sibthorpe PEM, Fitzgerald DM, Chen L, Sillence MN, de Laat MA.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 carbohydr...
McLean NL, McGilchrist N, Nielsen BD.Racehorses are often supplemented extra iron with the expectation that the iron will improve overall performance and health. A survey of 120 U.S. Thoroughbred trainers, representing 1978 Thoroughbreds from various regions of the U.S., was conducted to determine the average amount of dietary iron fed to Thoroughbred racehorses per day. Survey results indicated racehorses were fed an average of 3900 mg of iron per day from hay and grain alone. This exceeds the 0.8 mg/kg BW or 400 mg for a 500 kg working horse that the NRC 2007 recommends per day. Supplements increased the daily average intake of...
Gibson C, de Ruijter-Villani M, Stout TAE.In many species, the insulin-like growth factors (IGF1 and IGF2), their receptors and IGF binding proteins play important roles in preparing the endometrium for implantation, and regulating conceptus growth and development. To determine whether the IGF system may contribute to conceptus-maternal interaction during equine pre-implantation development, we evaluated mRNA expression for IGF system components in conceptuses, and endometrium recovered from pregnant and cycling mares, on days 7, 14, 21 and 28 after ovulation. We also investigated expression of IGF1, IGF2 and their receptors 6 and 11 ...
Dosi MCMC, McGorum BC, Kirton RD, Cillán-García E, Mellanby RJ, Keen JA, Hurst EA, Morgan RA.Vitamin D deficiency is common in humans and is increasingly linked to the pathogenesis of a multitude of diseases including obesity and metabolic syndrome. The biology of vitamin D in horses is poorly described; the relative contribution of the diet and skin synthesis to circulating concentrations is unclear and associations with the endocrine disease have not been explored. Objective: To determine the relationship between management, season and endocrine disease and vitamin D status in horses. Methods: Cross-sectional cohort study. Methods: Plasma concentrations of 25-hydroxyvitamin D2 (25(O...
Jorge-Smeding E, Warnken T, Grob AJ, Feige K, Pudert T, Leung YH, Go YY, Kenéz Á.Insulin dysregulation (ID) is a determinant of equine metabolic syndrome. Among the sphingolipids, ceramides contribute to the development of ID; however, the cross talk between the liver and adipose tissue (AT) depots and the variation among AT depots in terms of ceramide metabolism are not well understood. We aimed to characterize the sphingolipidome of plasma, liver, and AT (nuchal, NUAT; subcutaneous, SCAT; omental, OMAT; retroperitoneal, RPAT) and their associations with insulin response to oral glucose testing (OGT) in normoinsulinemic and hyperinsulinemic horses. Plasma, liver, and AT s...
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...
Loos CMM, McLeod KR, Vanzant ES, Stratton SA, Bohannan AD, Coleman RJ, van Doorn DA, Urschel KL.The objective of the study was to characterize the temporal changes of phosphorylation patterns of mTOR signaling proteins in response to two dietary protein sources in insulin dysregulated (ID, n = 8) and non-ID (n = 8) horses. Horses were individually housed and fed timothy grass hay and 2 daily concentrate meals so that protein was the first limiting nutrient and the total diet provided 120% of daily DE requirements for maintenance. On sample days, horses randomly received 0.25 g CP/kg BW of a pelleted alfalfa (AP) or commercial protein supplement (PS). Blood samples were collected before a...
Stefanovski D, Robinson MA, Van Eps A.Insulin dysregulation (ID) is the most important risk factor for the development of laminitis in horses and therapies to control it are needed. Objective: To assess the effects of a single dose of the synthetic GLP-1 analog exenatide on postprandial insulin dynamics. We hypothesized that exenatide would improve insulin sensitivity and lower postprandial blood insulin concentrations. Methods: Randomized, crossover, experimental study. Methods: Six horses (3 mares, 3 geldings; 2 with normal insulin regulation [NIR] and 4 with mild ID). Methods: Horses completed both study arms: subcutaneous admi...
Senderska-Płonowska M, Siwińska N, Zak-Bochenek A, Rykała M, Słowikowska M, Madej JP, Kaleta-Kuratewicz K, Niedźwiedź A.Obesity is a common problem in horses. The associations between obesity and equine metabolic syndrome (EMS) and between EMS and laminitis are known. However, there is a lack of data on whether obesity itself can affect hoof lamellae. Forelimbs and blood from 12 draft horses (six obese and six lean) from a slaughterhouse were acquired. To exclude laminitis and EMS horses, insulin concentration was measured, and hooves were radiographed. Histological evaluation was performed. The shape of the primary and secondary epidermal lamellae (PEL and SEL) was evaluated, and the length of the keratinized ...
Williams NJ, Furr M, Navas de Solis C, Campolo A, Davis M, Lacombe VA.Metabolic syndrome in humans is commonly associated with cardiovascular dysfunction, including atrial fibrillation and left ventricular diastolic dysfunction. Although many differences exist between human and equine metabolic syndrome, both of these conditions share some degree of insulin resistance. The aims of this pilot study were to investigate the relationship between insulin sensitivity and cardiac function. Seven horses (five mares, two geldings, aged 17.2 ± 4.2 years, weight 524 ± 73 kg) underwent insulin-modified frequently sampled intravenous glucose tolerance testing to determine ...
Salinas C, Espinosa G, Morales N, Henríquez C, Morán G, Gajardo G, Burgos RA, Uberti B.Obesity and insulin dysregulation (ID) are increasingly prevalent conditions in equid populations worldwide. Immune impairment is well described in humans with metabolic dysfunction and is reported but still incompletely understood in horses. This study evaluated the effect of acute induced transient hyperglycemia on apoptosis, phagocytosis and oxidative burst activity of peripheral blood polymorphonuclear cells (PMN) of lean and obese adult horses with or without insulin dysregulation. Seventeen adult horses were allocated into three groups based on their body condition score (BCS) and metabo...
Timko KJ, Hostnik LD, Watts MR, Chen C, Bercz A, Toribio RE, Belknap JK, Burns TA.Insulin dysregulation is a hallmark of equine metabolic syndrome (EMS) and increases the risk for development of laminitis. Accurate diagnosis of insulin dysregulation is crucial for implementation of preventative strategies in this population. The objective was to assess the effects of dexamethasone administration on insulin and glucose dynamics in light-breed horses and assess the agreement of various diagnostic tests for insulin dysregulation [basal [insulin] (BI), oral sugar test (OST), and combined glucose-insulin test (CGIT)]. Fourteen adult light-breed horses. Prospective, experimental ...
Loos CMM, Urschel KL, Vanzant ES, Oberhaus EL, Bohannan AD, Klotz JL, McLeod KR.The objectives of the study were to study the effects of the synthetic ergot alkaloid (EA), bromocriptine, on glucose and lipid metabolism in insulin dysregulated (ID, n = 7) and non-ID (n = 8) mares. Horses were individually housed and fed timothy grass hay and two daily concentrate meals so that the total diet provided 120% of daily DE requirements for maintenance. All horses were given intramuscular bromocriptine injections (0.1 mg/kg BW) every 3 days for 14 days. Before and after 14 days of treatment horses underwent a combined glucose-insulin tolerance test (CGIT) to assess insulin sensit...
Lovett AL, Gilliam LL, Sykes BW, McFarlane D.Both obesity and metabolic syndrome are associated with hypercoagulability in people, increasing the risk of cardiovascular disease and thromboembolic events. Whether hypercoagulability exists in obese, insulin-dysregulated horses is unknown. Objective: To determine if coagulation profiles differ between healthy horses and those with obesity and insulin dysregulation. Methods: Fifteen healthy horses (CON) and 15 obese, insulin-dysregulated horses (OBID). Individuals were university or client owned. Methods: Case-control study. Obesity was defined as a body condition score (BCS) ≥7.5/9 (modif...
Macon EL, Harris P, Barker VD, Adams AA.Seasonal effects on the oral sugar test (OST), used to monitor insulin dysregulation (ID) status to help reduce laminitis risk, are poorly understood in the ID horse. Resting, (basal) insulin (T0) and 60-minute (T60) OST (0.15 mL/Kg BW Karo Light Corn Syrup) insulin responses were evaluated, once per each season over 2 years, in ID (n = 11 14.9 ± 4.3 years; mean ± SD) and non-insulin dysregulated (NID: n = 11 16.4 ± 5.3 years; mean ± SD) horses housed on the same farm. Seasonal morphometric measurements were collected: bodyweight (BW), body-condition scores (BCS), and cresty neck score...
Knowles EJ, Elliott J, Harris PA, Chang YM, Menzies-Gow NJ.Quantifying risk factors for laminitis development requires improvement. Objective: To identify the most useful physical examination, metabolic and management factors to predict laminitis development in client-owned, nonlaminitic ponies. Methods: Prospective cohort study. Methods: Physical examination, metabolic and management data were collected from a pony cohort 6 monthly for up to 4 years. Ponies were monitored for the development of laminitis. Metabolic data included basal plasma concentrations of ACTH ([ACTH]), adiponectin ([adiponectin]), triglycerides and glucose. Serum insulin concen...
Storms N, Medina Torres C, Franck T, Sole Guitart A, de la Rebière G, Serteyn D.Laminitis is a pathology of the equine digit leading to a failure of the dermo-epidermal interface. Neutrophil activation is recognized as a major factor in SIRS-associated laminitis. Less is known about the role of neutrophil activation in laminitis associated with metabolic disorders. The aim of this descriptive study was to observe whether myeloperoxidase is increased in the laminae during early stage laminitis in three horses subjected to a prolonged euglycemic hyperinsulinemic clamp (pEHC). After 48 h of pEHC-treatment, horses were subjected to euthanasia. Two healthy horses are used as c...
Sillence M, Meier A, de Laat M, Klee R, Reiche D.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 af...
Kinsella HM, Hostnik LD, Snyder HA, Mazur SE, Kamr AM, Burns TA, Mossbarger JC, Toribio RE.The equine neonate is considered to have impaired glucose tolerance due to delayed maturation of the pancreatic endocrine system. Few studies have investigated insulin sensitivity in newborn foals using dynamic testing methods. The objective of this study was to assess insulin sensitivity by comparing the insulin-modified frequently sampled intravenous glucose tolerance test (I-FSIGTT) between neonatal foals and adult horses. This study was performed on healthy neonatal foals (n = 12), 24 to 60 hours of age, and horses (n = 8), 3 to 14 years of age using dextrose (300 mg/kg IV) and insulin (0....
Fuentes-Romero B, Muñoz-Prieto A, Cerón JJ, Martín-Cuervo M, Iglesias-García M, Aguilera-Tejero E, Díez-Castro E.Obesity and its associated complications, such as metabolic syndrome, are an increasing problem in both humans and horses in the developed world. The expression patterns of resistin differ considerably between species. In rodents, resistin is expressed by adipocytes and is related to obesity and ID. In humans, resistin is predominantly produced by inflammatory cells, and resistin concentrations do not reflect the degree of obesity, although they may predict cardiovascular outcomes. The aim of this study was to investigate the usefulness of resistin and its relationship with ID and selected ind...
Rumfola E, Banse HE, Atkins M, McGowan CM, Ireland JL.Endocrinopathic laminitis is the most common cause of laminitis in the field. Insulin has recently been implicated as a key factor in development of endocrinopathic laminitis; however, it is unclear whether diagnostic, and treatment approaches reflect insights derived from recent research. This study sought to evaluate North American veterinary practitioners' approach to endocrinopathic laminitis in the field. Demographic information, approach to diagnosis, management, and prognosis of endocrinopathic laminitis, as well as factors influencing changes in approach to laminitis were collected. To...
Mendoza FJ, Buzon-Cuevas A, Toribio RE, Perez-Ecija A.Insulin dysregulation (ID) is diagnosed in horses and ponies using oral glucose (OGTT) and oral sugar (OSTT) tolerance tests. The enteroinsular axis plays a major role in postprandial glucose disposal and insulin response in horses, ponies and foals. The insulin and incretin response to oral carbohydrate challenges has not been characterised in donkeys. Objective: (a) To characterise OGTT and OSTT, and (b) to assess the plasma incretin response to OGTT and OSTT in healthy donkeys. Methods: In vivo experiments. Methods: Six healthy adult female Andalusian donkeys were challenged with OGTT (1 g...
Obesity has become a serious health problem with frequent occurrence both in human and animal populations. It is estimated that it may affect over 85% of the human population and 70-80% of horses and cows by 2030. Fat cow syndrome (FCS) is a combination of metabolic, digestive, infectious, and reproductive disorders that affects obese periparturient dairy cows, and occurs most frequently in loose-housing systems, where periparturient and dry cows are fed and managed in one group disregarding the lactation stages. Equine metabolic syndrome (EMS) was named after human metabolic syndrome (MetS) a...
Vaughn SA, Norton NA, Hart KA.Mechanisms resulting in breed predispositions to insulin dysregulation (ID) are poorly characterized. Cortisol antagonizes insulin, and free, biologically active cortisol can be increased in ID. Breed-related differences in serum free cortisol fraction (FCF) could contribute to ID, but FCF has not been quantified in equidae predisposed to ID, such as ponies. To compare FCF and other hypothalamic-pituitary-adrenal (HPA) axis hormones between horses and ponies during health and ID. We hypothesized: (1) FCF is higher in ponies than horses in health, and is higher still in ponies with ID and obes...
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...
Grenager NS.Endocrinopathic laminitis (EL) primarily occurs because of insulin dysregulation (ID) mediated through downstream effects of insulin on IGF-1R in lamellar tissues. There is likely contributing vascular and metabolic dysfunction within the lamellae, but EL is relatively non-inflammatory. EL is associated with lamellar stretching, proliferation, and failure, ultimately causing failure of the suspensory apparatus of the distal phalanx. Proper education regarding mitigating risk factors makes this a largely preventable cause of laminitis. Annual hoof evaluation plus screening geriatric horses for ...
Lyn Macon E, Harris P, Partridge E, Day Barker V, Adams A.The oral sugar test (OST) is frequently used to identify insulin dysregulated (ID) equines. The effect of fasting and varying sugar dose for the OST has been investigated in the pony but little work has been done in the horse. This study aimed to investigate (1) an OST response with access to forage continued until the time of the OST or prevented for 3 hours prior to the OST and (2) responses of ID and non-insulin dysregulated (NID) horses to two different OST doses. Twenty-one mixed-breed horses (14.8 ± 3.2 years; 574.3 ± 83.3 kg) were used in two randomized crossover studies. Seven ID and...
Knowles EJ, Harris PA, Elliott J, Menzies-Gow NJ.It is recommended that the oral sugar test (OST) for insulin dysregulation (ID) be performed after an overnight fast, but fasting is impractical in ponies kept solely at pasture. There are few data on OST repeatability and reliability in ponies. Objective: To report 1) whether OST results obtained in the morning after an overnight fast or without fasting in the afternoon (FASTING/FED) can be used interchangeably, 2) time of highest insulin concentration T [insulin], repeatability and reliability of insulin response to the OST when FASTING or FED and 3) dichotomous agreement (ID/normal) within ...
Yoon MJ, Berger T, Roser JF.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...
Lacombe VA.Glucose uptake is the rate-limiting step in glucose utilization in mammalians and is tightly regulated by a family of specialized proteins, called the facilitated glucose transporters (GLUTs/SLC2). GLUT4, the major isoform in insulin-responsive tissue, translocates from an intracellular pool to the cell surface and as such determines insulin-stimulated glucose uptake. However, despite intensive research over 50 years, the insulin-dependent and -independent pathways that mediate GLUT4 translocation are not fully elucidated in any species. Insulin resistance (IR) is one of the hallmarks of equin...
Beech J, Boston RC, McFarlane D, Lindborg S.To measure plasma ACTH, alpha-melanocyte-stimulating hormone (aloha-MSH), and insulin concentrations during various photoperiods between February and October in horses and ponies with and without pituitary pars intermedia dysfunction (PPID). Methods: Cohort study. Methods: 13 clinically normal (control) ponies, 14 clinically normal (control) horses, 7 ponies with PPID, and 8 horses with PPID. Methods: Blood samples were collected from February through October during 8 photoperiods: 1, February 13 through March 2; 2, April 4 through 6; 3, June 19 through 22; 4, August 6 through 7; 5, August 14 ...
Smith S, Harris PA, Menzies-Gow NJ.The in-feed oral glucose test (OGT) and oral sugar test (OST) are advocated as field tests of insulin sensitivity in horses and ponies but have not been directly compared. Objective: To compare the insulin response to OGT and OST in 8 ponies and 5 horses of unknown insulin sensitivity. Methods: Experimental, randomised crossover study. Methods: Animals were fasted for 8 h overnight before and throughout testing. They were fed 1 g/kg bwt glucose powder with chaff (OGT) or 0.15 ml/kg bwt corn syrup (Karo™ Light Syrup; OST) was administered per os in a randomised crossover study with 48...
McGowan CM, Frost R, Pfeiffer DU, Neiger R.Serum insulin concentration and its use as a prognostic indicator in horses with equine Cushing's syndrome (ECS) have been poorly documented. Objective: To examine daily insulin variations in horses with ECS and the effect of treatment using trilostane, a competitive inhibitor of 3beta-hydroxysteroid dehydrogenase. Further, we aimed to examine the relationship between baseline serum insulin concentration and survival in horses with ECS. Methods: Basal serum insulin concentrations were measured in 20 confirmed ECS cases by taking blood at regular 4 h intervals for 24 h (1200, 1600, 2000, 2400, ...
Geor RJ, Harris P.Insulin resistance (IR) and hyperinsulinemia increase risk for development of laminitis in horses and ponies. Obesity also has been associated with heightened risk for laminitis, likely by means of development of IR. Dietary factors, particularly the nonstructural carbohydrate (NSC) load, modulate risk for laminitis in these animals by means of exacerbation of IR or gastrointestinal disturbances that trigger the condition. Specific dietary management strategies to lessen risk for laminitis include caloric restriction to promote weight loss and improve insulin sensitivity in obese animals and s...
Waller AP, Burns TA, Mudge MC, Belknap JK, Lacombe VA.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...
Treiber KH, Boston RC, Kronfeld DS, Staniar WB, Harris PA.Insulin resistance has been suggested to increase the risk of certain diseases, including osteochondrosis and laminitis. Our objective was to evaluate the effect of adaptation to high-glycemic meals on glucose-insulin regulation in healthy Thoroughbred weanlings. Twelve Thoroughbred foals were raised on pasture and supplemented twice daily with a feed high in either sugar and starch (SS; 49% nonstructural carbohydrates, 21% NDF, 3% crude fat on a DM basis) or fat and fiber (FF; 12% nonstructural carbohydrates, 44% NDF, 10% crude fat on a DM basis). As weanlings (age 199 +/- 5 d; BW 274 +/- 5 k...
Gentry LR, Thompson DL, Gentry GT, Davis KA, Godke RA, Cartmill JA.An experiment was conducted to determine the effects of high vs low body condition scores (BCS) produced by restricted feeding on reproductive characteristics, hormonal secretion, and leptin concentrations in mares during the autumnal transition and winter anovulatory period. Mares with BCS of 6.5 to 8.0 were maintained on pasture and/or grass hay, and starting in September, were full fed or restricted to produce BCS of 7.5 to 8.5 (high) or 3.0 to 3.5 (low) by December. All but one mare with high BCS continued to ovulate or have follicular activity during the winter, whereas mares with low BCS...
Morgan RA, Keen JA, McGowan CM.Treatment of equine metabolic syndrome (EMS) is essential to improve insulin sensitivity and reduce the risk of laminitis. Calorie restriction and increased exercise are the mainstays of treatment but there is potential for poor owner compliance. Objective: To determine whether significant weight loss accompanied by improvements in measures of insulin sensitivity can be achieved in horses and ponies with EMS managed by their owners in their normal environment under veterinary guidance. Methods: Retrospective clinical case series. Methods: Horses and ponies attending 2 university hospitals for ...
Tinworth KD, Wynn PC, Boston RC, Harris PA, Sillence MN, Thevis M, Thomas A, Noble GK.Determining circulating equine insulin concentrations is becoming increasingly important in equine clinical practice and research. Most available assays are optimized for human medicine, but there is strong equine cross-reactivity because of the highly conserved nature of insulin. To identify an accurate and reliable assay for equine insulin, 6 commercial immunoassays were evaluated for precision, accuracy, and specificity. Only 1 assay initially reached the requisite standard: Mercodia Equine Insulin Enzyme-linked Immunosorbent assay (ELISA). Plasma matrix interferences were identified when t...
Helmstaedter V, Feurle GE, Forssmann WG.Equine pancreas was investigated with immunohistochemical methods to study the distribution of endocrine cells immunoreactive to anti-insulin, anti-glucagon, and anti-somatostatin. A-cells demonstrable by anti-glucagon are located in the center of Langerhans islets and frequently in the duct epithelium. Few A-cells are seen associated to acini. Anti-insulin reactive B-cells form a large zone around the center of the Langerhans islets in which some B-cells lie between exocrine cells and others, although few, are located in the duct epithelium. D-cells stained with anti-somatostatin serum form a...
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...
Sessions-Bresnahan DR, Schauer KL, Heuberger AL, Carnevale EM.Obesity is associated with disrupted reproductive cycles in mares, but the impact of obesity on follicles and oocytes has received minimal attention. We investigated the impact of obesity on 1) expression of selected genes in follicle cells for carbohydrate metabolism, inflammatory cytokines, lipid homeostasis, endoplasmic reticulum stress, and mitochondrial function; 2) follicular fluid content of metabolic hormones and metabolites; and 3) lipid fingerprint of oocytes. Mares (9-13 yr) were classified as control (n = 8, normal weight, body condition score [BCS] 5.1, 10.4% body fat) or obese (n...
Place NJ, McGowan CM, Lamb SV, Schanbacher BJ, McGowan T, Walsh DM.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...
Karikoski NP, Patterson-Kane JC, Singer ER, McFarlane D, McGowan CM.Hoof lamellar pathology in horses with pituitary pars intermedia dysfunction (PPID) has not been described previously. Objective: To describe the histomorphometry and pathological lesions in hoof lamellar tissue of animals that had PPID with or without concurrent laminitis, with reference to age-matched controls. We hypothesised that lamellar lesions consistent with laminitis would be associated with PPID, even in animals without current or historical laminitis. Methods: Prospective case-control study. Methods: Mid-dorsal hoof histological sections were obtained post mortem from the forelimbs ...
Powell DM, Reedy SE, Sessions DR, Fitzgerald BP.Twelve untrained aged mares were used to determine whether 7 days of light exercise improved peripheral tissue insulin sensitivity. Mares were divided into obese-exercised (n = 3), obese-sedentary (n = 3), lean-exercised (n = 3) and lean-sedentary (n = 3) groups. The exercised groups were worked at a trot to a heart rate (HR) of not more than 140 beats/min for 30 min in a round pen. Each group was subjected to 3 euglycaemic hyperinsulinaemic clamps: prior to exercise (P), 24 h following the seventh exercise training session (E) and 9 days postexercise training (PE). Prior to exercise training,...
Durgam SS, Stewart AA, Pondenis HC, Gutierrez-Nibeyro SM, Evans RB, Stewart MC.To compare in vitro expansion, explant colonization, and matrix synthesis of equine tendon- and bone marrow-derived cells in response to insulin-like growth factor-I (IGF-I) supplementation. Methods: Cells isolated from 7 young adult horses. Methods: Tendon- and bone marrow-derived progenitor cells were isolated, evaluated for yield, and cultured on autogenous cell-free tendon matrix for 7 days. Samples were analyzed for cell viability and expression of collagen type I, collagen type III, and cartilage oligomeric matrix protein mRNAs. Collagen and glycosaminoglycan syntheses were quantified ov...
Jacob SI, Geor RJ, Weber PSD, Harris PA, McCue ME.Glucose and insulin dynamics may be different in adult and aged horses. Objective: To determine the effects of age and dietary carbohydrates on glucose and insulin dynamics in healthy horses. Methods: Balanced Latin square with four isocaloric diets: CONTROL (hay plus restricted-starch-and-sugar fortified pellets), STARCH (control plus kibbled corn), FIBER (control plus unmolassed sugar beet pulp/soybean hull pellets) and SUGAR (control plus dextrose powder). Methods: A total of 16 healthy Thoroughbreds and Standardbreds divided into two age groups: ADULT (8.8 ± 2.9 years; n = 8) and AGE...
de Laat MA, Hampson BA, Sillence MN, Pollitt CC.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. Objective: 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). Methods: Eight, university-owned, mixed-breed, adult ponies with body condition scores (BCS) ≥5/9 were used. Metho...
Donaldson MT, LaMonte BH, Morresey P, Smith G, Beech J.Medical records of 27 horses (including 13 ponies) treated with pergolide or cyproheptadine for pituitary pars intermedia dysfunction were reviewed to determine the effect of treatment on plasma ACTH, insulin, and glucose concentrations and clinical signs. Prior to treatment, the most common clinical signs were laminitis, hirsutism, and abnormal body fat distribution. The median pergolide dose was 3.0 microg/kg p.o. q24h (range, 1.7-5.5 microg/kg). All horses treated with cyproheptadine were given 0.25 mg/kg p.o. q24h. After pergolide treatment, ACTH concentrations (n = 20; median = 30.4 pg/ml...
Marycz K, Szłapka-Kosarzewska J, Geburek F, Kornicka-Garbowska K.Equine metabolic syndrome (EMS) is characterized by adiposity, insulin dysregulation and increased risk for laminitis. Increased levels of specific liver enzymes in the peripheral blood are typical findings in horses diagnosed with EMS. Current management of EMS is based on caloric restriction and increased physical activity. However, new potential treatment options are arising such as the transplantation of autologous adipose stem cells (ASC). However, cytophysiological properties of ASC derived from EMS horses are impaired which strongly limits their therapeutic potential. We hypothesized, t...
Meier A, Reiche D, de Laat M, Pollitt C, Walsh D, Sillence M.There are no registered veterinary drugs for treating insulin dysregulation and preventing insulin-associated laminitis in horses. Velagliflozin is a sodium-glucose co-transport 2 inhibitor that reduces renal glucose reabsorption, promotes glucosuria, and consequently, decreases blood glucose and insulin concentrations. This study aimed to determine if velagliflozin reduced hyperinsulinemia and prevented laminitis in insulin-dysregulated ponies fed a challenge diet high in non-structural carbohydrates (NSC). An oral glucose test (1 g dextrose/kg BW) was used to screen 75 ponies for insulin dys...
Frank N, Elliott SB, Chameroy KA, Tóth F, Chumbler NS, McClamroch R.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...
Waller AP, Kohler K, Burns TA, Mudge MC, Belknap JK, Lacombe VA.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...
Borer-Weir KE, Bailey SR, Menzies-Gow NJ, Harris PA, Elliott J.To evaluate a human radioimmunoassay (RIA) and equine and high-range porcine (hrp) species-specific ELISAs for the measurement of high serum insulin concentrations in ponies. Methods: Serum samples from 12 healthy nonobese ponies (7 clinically normal and 5 laminitis prone; 13 to 26 years of age; 11 mares and 1 gelding) before and after glucose, insulin, and dexamethasone administration. Methods: Intra-and interassay repeatability, freeze-thaw stability, dilutional parallelism, and assay agreement were assessed. Results: Assay detection limits were as follows: RIA, < 389 μU/mL; equine ELISA...
Bamford NJ, Baskerville CL, Harris PA, Bailey SR.The enteroinsular axis is a complex system that includes the release of incretin hormones from the gut to promote the absorption and utilization of glucose after a meal. The insulinogenic effect of incretin hormones such as glucagon-like peptide-1 (GLP-1) remains poorly characterized in the horse. The aim of this study was to compare postprandial glucose, insulin, and GLP-1 responses of different equine breeds adapted to twice-daily meals containing micronized maize. Four Standardbred horses, 4 mixed-breed ponies, and 4 Andalusian cross horses in moderate BCS (5.5 ± 0.2 out of 9) were fed mea...
Hodavance MS, Ralston SL, Pelczer I.Metabonomic analysis is a powerful tool for identifying and characterizing metabolic disorders, for example type 2 diabetes and the metabolic syndrome. Nuclear magnetic resonance (NMR) spectroscopy is an essential tool for such analysis, with special benefits. The review assesses the current status and potential of NMR-based metabonomics of type 2 diabetes. The horse is proposed as a possible model for studying this condition and disease. Some examples are shown of horse blood analyses by NMR.
Schreiber CM, Stewart AJ, Kwessi E, Behrend EN, Wright JC, Kemppainen RJ, Busch KA.To determine whether seasonal variations exist in endogenous plasma ACTH, plasma α-melanocyte-stimulating hormone (α-MSH), serum cortisol, and serum insulin concentrations and in the results of a dexamethasone suppression test for older, clinically normal geldings in Alabama. Methods: Cohort study. Methods: 15 healthy mixed-breed geldings (median age, 14 years). Methods: Sample collection was repeated monthly for 12 months. Dexamethasone (0.04 mg/kg [0.02 mg/lb], IM) was administered and cortisol concentrations were determined at 15 and 19 hours. Radioimmunoassays were used to measure ACTH, ...
