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.
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...
Horn R, Bamford NJ, Afonso T, Sutherland M, Buckerfield J, Tan RHH, Secombe CJ, Stewart AJ, Bertin FR.Pituitary pars intermedia dysfunction (PPID) is a commonly described endocrine disorder in higher latitudes of the Northern hemisphere but the description of the disease at lower latitudes and in the Southern hemisphere is limited. Objective: Document the clinical features of PPID at different Australian latitudes and climates, and investigate factors associated with survival, laminitis and insulin dysregulation (ID). Methods: Retrospective study of 274 equids from eight institutions across Australia. Methods: A diagnosis of PPID was based on endogenous ACTH, overnight dexamethasone suppressio...
Fitzgerald DM, Walsh DM, Sillence MN, Pollitt CC, de Laat MA.Supraphysiological insulin and incretin responses to a cereal-based diet have been described in horses and ponies with insulin dysregulation (ID). However, the hormonal responses to grazing have not yet been described. Objective: To determine if there is a difference in the insulin and incretin responses to grazing pasture between insulin-dysregulated and healthy ponies. Methods: A cohort of 16 ponies comprising 5 with normal insulin regulation (NIR), 6 with moderate ID (MID), and 5 with severe ID (SID). Methods: In this case-control study, an oral glucose test (OGT) was used to determine the ...
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...
Durward-Akhurst SA, Schultz NE, Norton EM, Rendahl AK, Besselink H, Behnisch PA, Brouwer A, Geor RJ, Mickelson JR, McCue ME.Equine Metabolic Syndrome (EMS) is characterized by abnormalities in insulin regulation, increased adiposity and laminitis, and has several similarities to human metabolic syndrome. A large amount of environmental variability in the EMS phenotype is not explained by commonly measured factors (diet, exercise, and season), suggesting that other environmental factors play a role in EMS development. Endocrine disrupting chemicals (EDCs) are associated with metabolic syndrome and other endocrine abnormalities in humans. This led us to hypothesize that EDCs are detectable in horse plasma and play a ...
DeBoer ML, Hathaway MR, Weber PSD, Sheaffer CC, Kuhle KJ, Martinson KL.Spring and late fall grazing can lead to metabolic problems in horses (Equus caballus L.) as a result of elevated nonstructural carbohydrates (NSC) in pastures. Therefore, the objectives were to determine the impact of different forage species on blood glucose and insulin concentrations of horses during the spring and late fall. Research was conducted in May (spring) and October (late fall) in St. Paul, MN. Alfalfa (Medicago sativa L.) and mixed perennial cool-season grasses (CSG) were grazed in spring, and CSG and teff (Eragrostis tef [Zucc.] Trotter) were grazed in late fall by six adult hor...
Cárceles-Rodríguez CM, Fernández-Varón E, Martín-Gimenez T, Aguirre C, Arion A, Rodríguez MJ, Ayala I.Insulin dysregulation (ID) is a common metabolic disorder in horses. Recently, incretin hormone release has been suggested to be involved in ID in horses. In human medicine, metformin and sitagliptin are commonly used in combination for metabolic syndrome. This combination could be useful in treating ID in horses. However, no pharmacokinetics data have been reported in this species. The objective of the present study was to establish the plasma concentration-time profile and to derive pharmacokinetics data for a combination of metformin and sitagliptin in horses after enteral administration. S...
Alicka M, Marycz K.Metabolic syndrome (MetS) is highly associated with a modern lifestyle. The prevalence of MetS has reached epidemic proportion and is still rising. The main cause of MetS and finally type 2 diabetes occurrence is excessive nutrient intake, lack of physical activity, and inflammatory cytokines secretion. These factors lead to redistribution of body fat and oxidative and endoplasmic reticulum (ER) stress occurrence, resulting in insulin resistance, increase adipocyte differentiation, and much elevated levels of proinflammatory cytokines. Cellular therapies, especially mesenchymal stem cell (MSC)...
Biddle AS, Tomb JF, Fan Z.Due to modern management practices and the availability of energy dense feeds, obesity is a serious and increasingly common health problem for horses. Equine obesity is linked to insulin resistance and exacerbation of inflammatory issues such as osteoarthritis and laminitis. While the gut microbiome is thought to play a part in metabolic status in horses, bacterial communities associated with obesity have yet to be described. Here we report differences in metabolic factors in the blood of obese, normal and lean horses correlated with differences in gut microbiome composition. We report that ob...
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...
Mendoza FJ, Gonzalez-Cara CA, Aguilera-Aguilera R, Toribio RE, Perez-Ecija A.Metabolic disorders are highly prevalent in donkeys. Differences in energy regulatory hormones and glucose dynamic testing, including the intravenous glucose tolerance test (IVGTT) and combined glucose-insulin test (CGIT), have been documented between donkeys and horses. The aims of this study were to characterise the insulin:glucagon (IGR) and glucagon:insulin (GIR) molar ratios, at baseline and in response to the IVGTT and CGIT in healthy donkeys, and to determine their correlation with endocrine (leptin, ghrelin and adiponectin) and morphometric variables. Median values and interquartile ra...
Kienzle E, Bockhorni T.The nutritional status of 36 patients with equine pituitary pars intermedia dysfunction (PPID) under pergolide treatment was investigated. Methods: The body condi tion score (BCS) and feeding were determined at the beginning of the study and after 60 and 120 days. Sampled blood for control of pergolid therapy were used for insulin and glucose measurement. A standardized questionnaire regarding the symptoms of the disease, including hypertrichosis and weight change, was completed by the owners. Results: The mean BCS (scale of 1 = cachexia to 9 = grossly obese) was 3.1 ± 0.8 (large horses 2.7 ...
Lewis SL, Holl HM, Long MT, Mallicote MF, Brooks SA.Equine metabolic syndrome (EMS), like human metabolic syndrome, comprises a collection of clinical signs related to obesity, insulin dysregulation and susceptibility to secondary inflammatory disease. Although the secondary conditions resulting from EMS can be life-threatening, diagnosis is not straightforward and often complicated by the presence of other concurrent conditions like pituitary pars intermedia dysfunction (PPID). In order to better characterize EMS, we sought to describe the variation within, and correlations between, typical physical and endocrine parameters for EMS. Utilizing ...
de Laat MA, Kheder MH, Pollitt CC, Sillence MN.Hyperinsulinemia is a major risk factor for equine laminitis, a debilitating and painful foot condition. Sweet taste receptor (T1R2/3) inhibitors have been used to reduce the insulin and glucose responses to oral carbohydrates in other species. However, their effect in horses has not been investigated. It would be useful to be able to attenuate the large post-prandial insulin response that typically occurs when a carbohydrate-rich meal is fed to insulin-dysregulated horses. Here we have determined the efficacy of two T1R2/3 inhibitors, lactisole and Gymnema sylvestre, for reducing glucose upta...
Tadros EM, Fowlie JG, Refsal KR, Marteniuk J, Schott HC.Hyperinsulinaemia is the suspected component of insulin dysregulation having the strongest association with laminitis and occurs variably in equids with pituitary pars intermedia dysfunction (PPID). Objective: We hypothesised that magnitude of hyperinsulinaemia correlates with laminitis severity in PPID-affected equids. Furthermore, we hypothesised that owners can be unaware of chronic endocrinopathic laminitis. Methods: Cross-sectional study. Methods: Serum insulin concentrations, owner-reported laminitis history and radiographic evidence of laminitis were determined in 38 client-owned horses...
Nanayakkara SN, Rahnama S, Harris PA, Anderson ST, de Laat MA, Bailey S, Sillence MN.Although it is well established that equine laminitis can be triggered by extreme hyperinsulinemia, the mechanism of insulin action is not known. High concentrations of insulin lead to separation of the weight-bearing apparatus from the hoof wall and are associated with an increased cycle of cell death and proliferation in the lamellae. Gene expression and immunohistochemistry studies have indicated that the lamellae are sparsely populated with insulin receptors, whereas IGF-1 receptors (IGF-1R) are abundant, suggesting that the action of insulin may be mediated by insulin binding to the IGF-1...
Marycz K, Weiss C, Śmieszek A, Kornicka K.Mesenchymal stem cells (MSCs) are frequently used in both human and veterinary medicine because their unique properties, such as modulating the immune response and differentiating into multiple lineages, make them a valuable tool in cell-based therapies. However, many studies have indicated the age-, lifestyle-, and disease-related deterioration of MSC regenerative characteristics. However, it still needs to be elucidated how the patient's health status affects the effectiveness of MSC differentiation. In the present study, we isolated mesenchymal stem cells from adipose tissue (adipose-derive...
DeBoer ML, Hathaway MR, Kuhle KJ, Weber PSD, Reiter AS, Sheaffer CC, Wells MS, Martinson KL.Elevated nonstructural carbohydrate (NSC) values in pasture forages can cause adverse health effects in some horses (Equus caballus L.). The objectives of this study were to determine the impact of different forage species on blood glucose and insulin concentrations of horses throughout the grazing season. Research was conducted in July (summer) and September (fall) in St. Paul, MN. Alfalfa (Medicago sativa L.), mixed perennial cool-season grasses (CSG), and teff (Eragrostis tef [Zucc.] Trotter) pastures were grazed by six horses (24 ± 2 years) that were randomly assigned to one of three for...
Sandow C, Fugler LA, Leise B, Riggs L, Monroe WT, Totaro N, Belknap J, Eades S.Laminitis has a considerable impact on the equine industry. Endocrinopathic laminitis is the most common form and affected horses often have hyperinsulinaemia due to an underlying metabolic disorder. Objective: The aim of this study was to determine if insulin weakens the structural integrity of digital lamellae and to develop an ex vivo model for the study of hyperinsulinaemia-induced lamellar failure. Methods: Ex vivo experiment. Methods: Biomechanical testing was used to assess the structural integrity of lamellar explants exposed to either medium alone (control) or medium supplemented with...
Frank N.Equine athletes are affected by 2 major endocrine/metabolic disorders, insulin dysregulation (ID) and pituitary pars intermedia dysfunction. ID is a risk factor for laminitis in horses, which poses the greatest threat to performance because of the damage that it causes to hoof structures. This article includes an in-depth discussion of ID and other risk factors for laminitis that are grouped together as equine metabolic syndrome. As horses age, the risk of pituitary pars intermedia dysfunction increases, and this endocrine disorder may exacerbate preexisting ID and further increase the risk of...
Bertin FR, Ruffin-Taylor D, Stewart AJ.Systemic inflammation is a cause of insulin dysregulation in many species, but the insulin and glucose dynamics in adult horses diagnosed with systemic inflammatory response syndrome (SIRS) are poorly documented. Objective: In SIRS in horses, insulin and glucose dynamics will be altered and associated with survival. Methods: Adult horses diagnosed with SIRS admitted to a referral hospital. Methods: Prospective study enrolling horses diagnosed with SIRS in which serum insulin and glucose concentrations were measured. Horses were grouped by outcome (survival, hyperinsulinemia, and hyperglycemia)...
Pakkanen SAE, de Vries A, Raekallio MR, Mykkänen AK, Palviainen MJ, Sankari SM, Vainio OM.Romifidine, an α-2 adrenoceptor agonist, is a widely-used sedative in equine medicine. Besides the desired sedative and analgesic actions, α-2 adrenoceptor agonists have side effects like alterations of plasma concentrations of glucose and certain stress-related hormones and metabolites in various species. Vatinoxan (previously known as MK-467), in turn, is an antagonist of α-2 adrenoceptors. Because vatinoxan does not cross the blood brain barrier in significant amounts, it has only minor effect on sedation induced by α-2 adrenoceptor agonists. Previously, vatinoxan is shown to prevent th...
Kenéz Á, Warnken T, Feige K, Huber K.Insulin dysregulation in horses is a metabolic condition defined by high insulin concentrations in the blood and peripheral insulin resistance. This hyperinsulinemia is often associated with severe damage in the hooves, resulting in laminitis. However, we currently lack detailed information regarding the potential involvement of particular metabolic pathways in pathophysiological causes and consequences of equine insulin dysregulation. This study aimed to assess the dynamic metabolic responses given to an oral glucose test (OGT) in insulin-sensitive and insulin-dysregulated horses by a targete...
Williams T, Rude B, Liao S, Mochal-King C, Nicodemus M.The objective of this study was to observe how fat incorporated into an equine forage-based diet through supplementation altered levels of plasma glucose, insulin and fatty acids. Five Shetland/Hackney cross pony mares were fed alfalfa pellet diets top dressed with commercially available vegetable oil (blend of soya bean, canola and corn oils) at 0%, 5%, 10% or 15% of diet. Ponies were randomly assigned one of four diets to start, with a 14-day adjustment period between transitioning to another one of the four diets. Ponies were gradually adapted to the new diet within the 14-day period before...
Lindåse S, Müller C, Nostell K, Bröjer J.Information about the effect of nonstructural carbohydrates (NSCs) in forage on the postprandial glucose and insulin response in horses is scarce. This is of interest as postprandial hyperinsulinemia in horses is a risk factor for laminitis. In addition, insulin sensitivity (IS) differs between breeds. The aim was to evaluate the postprandial glucose and insulin response to haylage diets with different NSC content in horses of 2 different breeds and to evaluate the relationship between the postprandial insulin response and measures of IS derived from a frequently sampled intravenous glucose to...
Carslake HB, Argo CM, Pinchbeck GL, Dugdale AHA, McGowan CM.Reduction of the hyperinsulinaemic response to feeding is central to the management of insulin dysregulation (ID). The aim of this study was to compare insulinaemic and glycaemic responses to soaked hay, dry hay and haylage in ponies. Twelve ponies of mixed breeds were maintained under identical management conditions. A randomised four-way crossover trial was conducted, in which fasted animals were fed a meal of 0.25% body weight as dry matter intake soaked hay, dry hay or haylage, or administered an oral glucose test (OGT). Blood glucose and serum insulin concentrations were measured before a...
de Laat MA, Fitzgerald DM, Sillence MN, Spence RJ.Equine insulin dysregulation (ID) is a common and poorly understood disorder that increases the risk of laminitis. Recent data show that the condition may be associated with alteration of the enteroinsular axis and enhanced glucose bioavailability. Upregulation of glucagon-like peptide-2 (GLP-2), an intestinotrophic peptide, leads to enhanced nutrient uptake and metabolic dysfunction in other species. Objective: The study aimed to 1) determine whether GLP-2 is differentially expressed in insulin-dysregulated ponies, compared with healthy ponies, and 2) confirm intestinal expression of the GLP-...
Urayama S, Arima D, Mizobe F, Shinzaki Y, Nomura M, Minamijima Y, Kusano K.Although hyperglycemia at admission with colic has been reported to have a poor prognosis, there is no report specifically about acute colitis with systemic inflammatory response syndrome (SIRS) in horses. In this study, we measured blood glucose (Glu), insulin (Ins), and cortisol (Cor) levels in 17 Thoroughbred racehorses diagnosed as having acute colitis with SIRS, and examined the relationship between time-dependent changes in Glu, Ins, and Cor and prognosis. Glu levels were high in 3 horses at admission, but thereafter no horses had persistently high Glu levels. There was no significant di...
Jacob SI, Murray KJ, Rendahl AK, Geor RJ, Schultz NE, McCue ME.Metabolomics, the study of small-molecule metabolites, has increased understanding of human metabolic diseases, but has not been used to study equine metabolic syndrome (EMS). Objective: (1) To examine the serum metabolome of Welsh Ponies with and without insulin dysregulation before and during an oral sugar test (OST). (2) To identify differences in metabolites in ponies with insulin dysregulation, obesity, or history of laminitis. Methods: Twenty Welsh Ponies (mean ± SD; 13.8 ± 9.0 years) classified as non-insulin dysregulated [CON] (n = 10, insulin 60 mU/L) at 75 minutes ...
Spelta CW.Equine pituitary pars intermedia dysfunction (PPID) is a neurodegenerative disease of the hypothalamus, resulting in the loss of dopaminergic inhibition of pars intermedia. An oxidative stress injury of unknown etiology has been suggested to initiate the neurodegeneration. While hypertrichosis (formerly known as hirsutism) is considered pathognomic for advanced disease, the antemortem diagnosis of subclinical and early disease has continued to prove difficult. Numerous tests have been used with varying sensitivities and specificities. The overnight dexamethasone suppression test, originally do...
Fitzgerald DM, Spence RJ, Stewart ZK, Prentis PJ, Sillence MN, de Laat MA.The equine microbiome can change in response to dietary alteration and may play a role in insulin dysregulation. The aim of this study was to determine the effect of adding pasture to a hay diet on the faecal bacterial microbiome of both healthy and insulin-dysregulated ponies. Faecal samples were collected from 16 ponies before and after dietary change to enable bacterial 16S rRNA sequencing of the V3-V4 region. The dominant phyla in all samples were the Firmicutes and Bacteroidetes. The evenness of the bacterial populations decreased after grazing pasture, and when a pony was moderately insu...
Sime A, McKellar Q, Nolan A.A serum-free cell culture method was developed for equine tracheal epithelial cells which allowed the growth and characterisation of the phenotypical properties of this cell type. Several variables influenced the efficacy of the attachment and growth of the isolated cells. Serum and a collagen matrix were essential components for efficient cell attachment. Once attachment had occurred, cell growth was enhanced by a serum-free medium containing bovine pituitary extract, retinoic acid, insulin, hydrocortisone, transferrin, epidermal growth factor, adrenaline and triiodothyronine. The mean time t...
George LA, Staniar WB, Cubitt TA, Treiber KH, Harris PA, Geor RJ.To characterize the effects of pregnancy on insulin sensitivity (SI) and glucose dynamics in pasture-maintained mares fed supplemental feeds of differing energy composition. Methods: Pregnant (n = 22) and nonpregnant (10) healthy Thoroughbred mares. Methods: Pregnant and nonpregnant mares underwent frequently sampled intravenous glucose tolerance tests at 2 times (period 1, 25 to 31 weeks of gestation; period 2, 47 weeks of gestation). Following period 1 measurements, mares were provided a high-starch (HS; 39% starch) or high-fat and -fiber (14% fat and 70% fiber) supplemental feed. From a sub...
Suagee JK, Corl BA, Wearn JG, Crisman MV, Hulver MW, Geor RJ, McCutcheon LJ.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 = ...
Nourian AR, Asplin KE, McGowan CM, Sillence MN, Pollitt CC.Anatomical changes in the hoof lamellar tissue induced by prolonged hyperinsulinaemia have not been described previously. Analysis of the induced lesions may promote understanding of hyperinsulinaemic laminitis pathogenesis and produce clinical benefit. Objective: To use light and transmission electron microscopy (TEM) to document hoof lamellar lesions in ponies clinically lame after prolonged hyperinsulinaemia. Methods: Nine clinically normal, mature ponies were allocated randomly to either a treatment group (n = 5) or control group (n = 4). The treatment group received insulin via a modified...
Kheder MH, Sillence MN, Bryant LM, de Laat MA.Metabolic disease is a significant problem that causes a range of species-specific comorbidities. Recently, a better understanding of glucose-dependent insulinotropic polypeptide (GIP) biology has led to the suggestion that inhibiting its action may attenuate obesity in several species. In horses, antagonism of GIP may also reduce hyperinsulinemia, which leads to insulin-associated laminitis, a painful comorbidity unique to this species. However, little is known about GIP in horses. The aims of this study were to examine the tissue distribution of equine GIP receptors (eGIPR), to determine whe...
Champion ZJ, Breier BH, Ewen WE, Tobin TT, Casey PJ.A survey of standardbred horses was conducted to build up a normal population profile for insulin like growth factor-I (IGF-I) concentrations in racing standardbreds and to ascertain how age, sex and geographic location affect IGF-I. Blood samples were drawn by jugular venepuncture from 202 racing standardbred horses aged one to eight years located in five different geographic regions of New Zealand. IGF-I concentrations were determined by insulin like growth factor-I binding protein (IGFBP)-blocked radioimmunoassay validated for the horse. As described in other species, age played a significa...
Durward-Akhurst SA, Schultz NE, Norton EM, Rendahl AK, Besselink H, Behnisch PA, Brouwer A, Geor RJ, Mickelson JR, McCue ME.Equine Metabolic Syndrome (EMS) is characterized by abnormalities in insulin regulation, increased adiposity and laminitis, and has several similarities to human metabolic syndrome. A large amount of environmental variability in the EMS phenotype is not explained by commonly measured factors (diet, exercise, and season), suggesting that other environmental factors play a role in EMS development. Endocrine disrupting chemicals (EDCs) are associated with metabolic syndrome and other endocrine abnormalities in humans. This led us to hypothesize that EDCs are detectable in horse plasma and play a ...
McFarlane D, Hill K, Anton J.Immunosuppression leading to opportunist bacterial infection is a well-recognized sequela of equine pituitary pars intermedia dysfunction (PPID). The mechanisms responsible for immune dysfunction in PPID however, are as of yet poorly characterized. Horses with PPID have high concentrations of hormones known to impact immune function including α-melanocyte stimulating hormone (α-MSH) and insulin. α-MSH and related melanocortins have been shown in rodents and people to impair neutrophil function by decreasing superoxide production (known as oxidative burst activity), migration and adhesion. T...
Stewart-Hunt L, Pratt-Phillips S, McCutcheon LJ, Geor RJ.Starch rich (S) feeds reduce insulin sensitivity in untrained horses when compared to high fat (F) feeds, but insulin sensitivity is not affected when S or F are fed during exercise training. The effects of S vs. F on training-associated alterations in skeletal muscle glucose metabolism are unknown. Objective: To determine the effects of dietary energy source on training-associated changes in insulin sensitivity, skeletal muscle GLUT4 protein and hexokinase (HK) and glycogen synthase (GS) activities in horses. Methods: After a baseline period on an all forage diet (Phase 1), horses were adapte...
Johnson PJ, Scotty NC, Wiedmeyer C, Messer NT, Kreeger JM.An 18-year-old Spanish Mustang mare was referred for evaluation of progressive weight loss and persistent hyperglycemia. Clinicopathologic abnormalities included marked hyperglycemia and glycosuria. Serum cortisol concentration was appropriately decreased following administration of dexamethasone, indicating that the horse did not have pituitary pars intermedia dysfunction. Serum insulin and plasma C-peptide concentrations were low, suggesting that hyperglycemia was a result of decreased secretion of insulin by pancreatic beta cells. In addition, glucose concentration did not return to the bas...
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...
Herrler A, Pell JM, Allen WR, Beier HM, Stewart F.Insulin-like growth factor-I (IGF-I) promotes early embryonic development in several species. In the rabbit, IGF-I binds to the embryonic coats from Day 3 of development onward by a 38-kDa protein that is probably insulin-like growth factor-binding protein 3 (IGFBP3). In the present study, ligand, Western, and Northern blot analyses were used to demonstrate the presence of IGF-I-binding activity, several immunoreactive IGFBP3 proteins, and IGFBP3 mRNA in horse conceptuses with particularly large amounts of immunoreactive IGFBP3 in the conceptus capsule. In addition, immunoprecipitation of radi...
Brennan KM, Urschel KL.Dexamethasone is an anti-inflammatory drug commonly used in equine medicine. Insulin sensitivity decreases with prolonged dexamethasone administration, but little information is available about the duration of this side effect after long-term treatment ends. Objective: To determine how long it takes for blood glucose, insulin and markers of insulin sensitivity to return to normal ranges after extended dexamethasone treatment has ceased. Methods: Experimental study. Methods: Eight healthy, mature, mixed-breed horses received 0.04 mg/kg bwt/day oral dexamethasone for 21 days. Blood samples wer...
Jackson BF, Goodship AE, Eastell R, Price JS.To evaluate changes in serum concentrations of biochemical markers of bone metabolism and insulin-like growth factor I (IGF-I) associated with treadmill exercise in young horses. Methods: 12 two-year-old Thoroughbred mares. Methods: During a 20-week study period, 6 horses were exercised on a treadmill 3 times a week (exercise group) and 6 horses received walking exercise 6 days a week (controls). Serum concentrations or activity of biochemical markers and IGF-I were assessed biweekly. Bone mineral density and content of the first phalanx were measured by dual-energy X-ray absorbiometry (DEXA) ...
Tinworth KD, Harris PA, Sillence MN, Noble GK.Insulin resistance and hyperinsulinaemia increase the risk of laminitis and horse owners and veterinarians should attempt to enhance insulin sensitivity in at-risk groups. In obese animals this may be achieved, in part, by promoting weight loss and increasing exercise, but such intervention may not be appropriate in non-obese insulin-resistant animals, or where exercise is contra-indicated for clinical reasons. An alternative approach to controlling insulin sensitivity in obese and non-obese horses may be the use of certain herbal compounds that have shown promise in humans and laboratory anim...
Xie L, Spencer ND, Beadle RE, Gaschen L, Buchert MR, Lopez MJ.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...
Rose RJ, Sampson D.Total and individual non-esterified fatty acids (NEFA), pyruvate, lactate, alpha ketoglutarate, acetoacetate, beta hydroxybutyrate, glucose and insulin were measured in horses during an 80 km endurance ride and during four days of food deprivation. In the latter group venous blood-gas and acid-base parameters, and plasma cortisol concentrations were also measured. During exercise and food deprivation the NEFA became considerably elevated, the predominant of which were oleic (35 per cent), palmitic (24 per cent), linoleic (19 per cent) and linolenic (10 per cent). By one hour after feeding tota...
Zak A, Siwinska N, Elzinga S, Barker VD, Stefaniak T, Schanbacher BJ, Place NJ, Niedzwiedz A, Adams AA.Age, neurodegenerative disorders, and dysfunction of insulin secretion may be correlated with increased systemic concentrations of acute phase markers. Thus, the study aimed to determine the effect of age, pituitary pars intermedia dysfunction (PPID), and insulin dysregulation (ID) associated with PPID, on markers of the acute phase reaction. Twenty-nine mix-breed horses of both sexes were classified into groups: (1) healthy adult controls, (2) healthy non-PPID geriatric horses, (3) PPID ID+ horses, and (4) PPID ID- horses. Whole blood proinflammatory cytokine gene expression and serum concent...
Gordon ME, McKeever KH, Bokman S, Betros CL, Manso-Filho H, Liburt N, Streltsova J.Horses in training tend to become inappetant; however, the mechanism responsible for this training-induced inappetance is not known. Objective: Training and/or ulcers alter the feed intake (FI) and hormonal and/or biochemical (active ghrelin, leptin, glucose, insulin and cortisol) responses to acute high intensity exercise. Methods: Eight Standardbred mares underwent 3 interval exercise tests (IET) and 3 parallel control tests (CON) before (IET1) and after 8 weeks of training (IET2) and after treatment for gastric ulcers (IET3). Plasma samples were taken before (0 min), during (last 10 sec of ...
Dühlmeier R, Deegen E, Fuhrmann H, Widdel A, Sallmann HP.To investigate the enteroinsular axis (EIA) in equines oral (oGTT) and intravenous (i.v.GTT) glucose tolerance tests (5.6 and 1 mmol glucose/kg BW, respectively) were performed with healthy, normal weight large horses and Shetland ponies. Plasma was analysed for concentrations of glucose, glucose-dependent insulinotropic polypeptide (GIP) and insulin. In all equines plasma GIP concentrations only increased significantly when glucose was administered orally. The insulin glucose ratio (IGR) was significantly higher during the oGTT than during the i.v.GTT in both races. Basal plasma glucose level...
Warnken T, Delarocque J, Schumacher S, Huber K, Feige K.Insulin dysregulation (ID) with basal or postprandial hyperinsulinemia is one of the key findings in horses and ponies suffering from the equine metabolic syndrome (EMS). Assessment of ID can easily be performed in clinical settings by the use of oral glucose challenge tests. Oral glucose test (OGT) performed with 1 g/kg bodyweight (BW) glucose administered via naso-gastric tube allows the exact administration of a defined glucose dosage in a short time. However, reliable cut-off values have not been available so far. Therefore, the aim of the study was to describe variations in insulin respo...
Martin-Gimenez T, de Blas I, Aguilera-Tejero E, Diez de Castro E, Aguirre-Pascasio CN.Equine metabolic syndrome (EMS) can be diagnosed by hormonal measurements; however, it would be important to find simpler measurements that allow easy identification of affected or at risk individuals. In horses, the dorsal neck region is one of the most frequent anatomical sites for fat deposition and neck obesity has been linked to EMS. The aim of this study was to evaluate the association of hormonal markers of obesity (leptin) and insulin resistance (insulin) with morphometric and ultrasonographic neck measurements in Andalusian horses. Plasma leptin and insulin concentrations were measure...
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...
DeBoer ML, Hathaway MR, Kuhle KJ, Weber PSD, Reiter AS, Sheaffer CC, Wells MS, Martinson KL.Elevated nonstructural carbohydrate (NSC) values in pasture forages can cause adverse health effects in some horses (Equus caballus L.). The objectives of this study were to determine the impact of different forage species on blood glucose and insulin concentrations of horses throughout the grazing season. Research was conducted in July (summer) and September (fall) in St. Paul, MN. Alfalfa (Medicago sativa L.), mixed perennial cool-season grasses (CSG), and teff (Eragrostis tef [Zucc.] Trotter) pastures were grazed by six horses (24 ± 2 years) that were randomly assigned to one of three for...
Urschel KL, Geor RJ, Waterfall HL, Shoveller AK, McCutcheon LJ.Providing protein or amino acid mixtures in combination with glucose to post exercise in man has resulted in increases in the post feeding insulin response and in muscle glycogen and protein synthesis rates. However, whether protein and/or amino acids can modify the post exercise insulin responses in horses remains to be fully elucidated. Objective: To determine whether whey protein or leucine addition to a glucose solution affects the post gavage plasma insulin, glucose and amino acid responses in horses and whether these responses are different following a period of exercise vs. rest. Method...
Kaske M, Elmahdi B, von Engelhardt W, Sallmann HP.It had been suggested that marked species differences in glucose tolerance tests were due to differences in insulin resistance. To compare insulin responsiveness, euglycemic hyperinsulinemic clamps were carried out in sheep, ponies, miniature pigs and camels. Porcine insulin was infused as primed-continuous infusions for 2 h (6 mU x kg(-1) x min(-1)). The steady state glucose infusion rates in the pigs, sheep, ponies and camels were 96.0, 18.6, 7.1 and 6.1 micromol x kg(-1) x min(-1), respectively. The maximal plasma insulin concentrations during the insulin infusions were 2,700 microU x ml(-1...
Peugnet P, Robles M, Mendoza L, Wimel L, Dubois C, Dahirel M, Guillaume D, Camous S, Berthelot V, Toquet MP, Richard E, Sandersen C, Chaffaux S....In stud management, broodmares are commonly fed concentrates in late pregnancy. This practice, however, was shown to correlate with an increased incidence of osteochondrosis in foals, which may be related to insulin sensitivity. We hypothesized that supplementation of the mare with barley in the last trimester of pregnancy alters the pre-weaning foal growth, glucose metabolism and osteoarticular status. Here, pregnant multiparous saddlebred mares were fed forage only (group F, n=13) or both forage and cracked barley (group B, n=12) from the 7th month of pregnancy until term, as calculated to c...
