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.
Andrews KE, Sibthorpe PEM, Fitzgerald DM, de Laat MA.Equine insulin dysregulation (ID) is a common condition that predisposes to hyperinsulinaemia-associated laminitis. Improved pathophysiological understanding would enable better management of ID and reduce the risk of laminitis. The incretin peptides, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), augment the insulin response to dietary glucose and GLP-1 has been implicated in the pathophysiology of ID. However, their temporal variation in response to a low-energy diet has not been reported. This study determined the variation in GLP-1, GIP and insulin ...
Viviani P, Ragno VM, Parker S, Montgomery JB.Endocrine disorders in horses, such as pituitary pars intermedia dysfunction and equine metabolic syndrome, rely on hormone testing for diagnosis, but seasonal and regional variabilities highlight the need for locally generated data. Objective: To characterize monthly blood concentrations of ACTH and insulin over 1 year in healthy horses in Saskatchewan. A secondary objective was to assess the association between these outcomes and the following factors: sex, age, breed, pregnancy status, level of exercise, body condition score, and cresty neck score. Methods: Sixty-eight clinically healthy, c...
Hallowell KL, van Eps AW, Kulp JC, Schnabel LV.Lipemia is a common comorbidity in horses with obesity or equine metabolic syndrome, but the impact of lipemia on the measurement of insulin and adiponectin has not been evaluated. Objective: To evaluate endogenous and exogenous lipemic interference with equine insulin and adiponectin measurements via several commercial assays. Methods: Endogenous lipemia was evaluated using plasma and serum samples with triglyceride concentrations of 1000 mg/dL (n = 6 each). Sample insulin concentrations were determined via fluorescence enzyme immunoassay (FEIA), ELISA, and lateral flow assay (LFA). ...
Vasco ACCM, Warren LK, Silva GM, Cuervo-Vivas W, Brandi RA, Silva VP, Lance JM, Dubeux JC, Wickens CL.Rhizoma peanut (RP, Arachis glabrata Benth) is an alternative legume forage to alfalfa (ALF, Medicago sativa L.) with less non-structural carbohydrates and crude protein. Yet, metabolic responses to consuming RP hay have never been evaluated in horses. Objective: The objective of this study was to investigate the effect of feeding RP 'Florigraze' hay on fecal and blood metabolic variables compared to alfalfa 'Legendary XHD' and bermudagrass (BMG, Cynodon dactylon L. 'Coastal') hays fed to maintenance horses. Methods: Six mature Quarter Horse geldings (596±40 kg) were randomly assigned to one ...
Satué K, Fazio E, Velasco-Martínez MG, Barbiera G, La Fauci D.Growth hormone (GH) influences follicular development mainly by stimulating insulin-like growth factor 1 (IGF-1), which acts systemically and locally within the ovary. However, the metabolic profile of follicular fluid (FF) in mares, particularly markers such as fructosamine (FRUCT), an indicator of glucose metabolism, remains poorly characterized. This study aimed to evaluate GH, IGF-1, and FRUCT concentrations in plasma and FF and their variation across follicle sizes. Sixty ovaries were collected during the breeding season from 30 clinically normal mares raised for meat production. Blood sa...
Teague P, Dark M, Verdugo D, Freeman D, McFarlane D.The equine pancreas remains understudied, particularly in the context of endocrine disease. This study aimed to characterize regional islet distribution and composition in the normal equine pancreas and investigate how hyperinsulinemia (HI) and pituitary pars intermedia dysfunction (PPID) influence pancreatic islet morphology and hormone expression. In the first experiment, pancreas samples from eight healthy horses were collected and analyzed across three anatomical locations: left lobe, body, and right lobe. The left lobe exhibited a greater relative islet area and perimeter compared to the ...
Page AE, McPeek JL, McGreevy E, Carattini S, Adam EN.Intra-articular (IA) corticosteroids can cause hyperinsulinemia, which can subsequently increase the risk of laminitis, particularly in horses with insulin dysregulation (ID). Sodium glucose cotransporter 2 inhibitors (SGLT2i), a drug class that is being utilised more commonly in horses with insulin dysregulation, could potentially be used to control post-IA corticosteroid hyperinsulinemia. Objective: To determine whether treatment with the SGLT2i drug ertugliflozin decreases hyperinsulinemia following intra-articular corticosteroid administration in metabolically normal horses. Methods: Prosp...
Rollet M, Flyps J, Vernemmen I, van Loon G, Schauvliege S.Hyperkalaemia is an uncommon complication of general anaesthesia in healthy horses. This case report describes the occurrence of life-threatening acute hyperkalaemia in a 13-year-old, female French Trotter anaesthetised for experimental right and left atrial 3D electro-anatomical mapping. Intra-operative development of hyperkalaemia (7.55 mmol/L) (Ref. 3.00-4.00 mmol/L) with atrial standstill on ECG necessitated transvenous ventricular pacing while initial treatment with insulin and glucose was initiated. Plasma potassium levels continued to increase (8.00 mmol/L) prompting adjunctive tr...
Mlyneková E, Zaťko S, Halo M, Imrich I, Halo M.This study aimed to examine the seasonal dynamics of non-structural carbohydrates in pasture and their relationship to metabolic indicators in horses with a history of laminitis. Thirty Hucul mares were divided into a laminitis group (LG, = 15) and a control group (CG, = 15). Insulin, glucose, fructosamines concentrations and body weight were monitored during four sampling periods (S0-S3), while pasture variables were analyzed during three periods (S1-S3). The concentration of water-soluble carbohydrates was highest in May (126.8 g/kg DM) and measured lower in October (57.9 g/kg DM), while s...
Ferreira C, Palhares MS, de Melo UP, Leme FOP, Maranhão RPA, Garcia HC, Gheller VA.Starvation and nutritional support clinically influence horses, particularly during the treatment of gastrointestinal diseases and post-surgical recovery. In this study, we aimed to evaluate the effects of different nutritional strategies on the endocrine response of horses subjected to exploratory laparotomy followed by food deprivation. Sixteen healthy adult horses were randomly allocated into four groups (n=4) based on treatments: enteral fluid therapy without (ENTFL) or with glutamine (ENTGL), and parenteral fluid therapy with glucose (PARFL) or total parenteral nutrition with glutamine (P...
Anger-Håål C, Fjordbakk CT, Ekstrand C, Skedsmo FS, Rørtveit R.Insulin dysregulation is a hallmark of equine metabolic syndrome (EMS), and in recent years, pharmacological treatment with sodium-dependent glucose transporter 2 inhibitors (SGLT2i) have shown promise in reducing the risk of hyperinsulinemia-associated laminitis in horses diagnosed with EMS. In humans and laboratory animals, this transporter protein is responsible for the majority of renal tubular glucose reabsorption, however, the presence of this and the related sodium-dependent glucose transporter 1 (SGLT1) have not yet been studied in equine kidneys. Additionally, studies in humans and la...
Page AE, McPeek JL, Carattini S, McGreevy E, Adam E.The goal of this project was to examine the metabolic effects of IA methylprednisolone acetate (MPA) following injection into multiple low-motion joints. Unassigned: Six 3-year-old geldings without pituitary pars intermedia dysfunction or insulin dysregulation were randomly injected with 20 mg of IA MPA/joint (80 mg total; bilateral distal hock joints) or an equal volume of saline. Serial blood samples were collected for resting ACTH, cortisol, insulin, and glucose, as well as insulin and glucose following repeated low-dose oral sugar tests. Treatments were crossed over after a 6-week washout,...
Norton EM, Plumb S, Shane D, Smalley L, McKendry K, Scharf B, Zemel M.Supplements claiming to improve metabolic profiles in equine metabolic syndrome (EMS) often lack scientific validation. Objective: To evaluate the effect of a supplement containing leucine, resveratrol and pyridoxine on the metabolic profile in ponies with EMS. Methods: Unmasked randomised, placebo-controlled field trial. Methods: Thirty-eight ponies completed the trial across five farms. Ponies were age and sex matched per farm and randomly assigned to the supplement (n = 20) or placebo group (n = 18) with owners masked to group assignments. Ponies were sampled at days -1/0 (T1), 7/8 ...
Donnelly CG, Peng S, Pflieger L, Manfredi J, Coleman M, Rappaport N, Price ND, Finno CJ.Metabolic syndrome (MetS)-encompassing obesity, insulin resistance, dyslipidemia, and hypertension-is prevalent in both humans and horses, offering a unique opportunity to explore shared pathophysiological mechanisms across species in a controlled model organism. In this first report from the Pioneer 100 Horse Health Project (P100HHP), we conducted a longitudinal, multi-omic analysis of 108 deeply phenotyped horses to interrogate individual health trajectories for precision insights into MetS. We identified two primary metabotypes: one characterized by elevated unsaturated triglycerides (TGs) ...
Horses maintained under traditional management systems and dependent on natural forages are often exposed to seasonal and compositional variations that can affect metabolic homeostasis. This study examined associations between forage nutrient composition and metabolic-morphometric indicators in horses from four agroecologically distinct regions of northwestern Romania. Eighty-eight horses managed under semi-extensive rural conditions underwent clinical examination, body condition scoring (BCS), cresty neck scoring (CNS), and fasting blood sampling. Forage samples ( = 34) from daily rations wer...
Bourebaba N, Domagała J, Bourebaba L.Equine metabolic syndrome (EMS) is associated with chronic low-grade inflammation, disruptions in mitochondrial dynamics and function, and an increased risk of developing laminitis. Recent research has highlighted that reduced levels of sex hormone-binding globulin (SHBG) in the bloodstream are linked to higher susceptibility to obesity, insulin resistance, and diabetes, potentially contributing to broader metabolic imbalances. This study aimed to evaluate whether exogenously administered SHBG could protect adipose-derived stem cells from horses affected by EMS (EqASC) against mitochondrial dy...
Bourebaba L, Panek M, Piedra LCC, Bourebaba N.Fetuin-A (FetA) is a multifactorial glycoprotein primarily synthesized by the liver with additional expression in adipose tissue, the abundance of which is tightly regulated by the FBXW7 E3 ubiquitin ligase. Recently, FetA has been implicated in the pathogenesis of insulin resistance and associated metabolic failures in humans through its potent and selective inhibition of insulin receptor tyrosine kinase activity, however, no studies have yet directly investigated its role in the development and progression of equine obesity. In this investigation, FetA levels were measured in serum, liver, a...
Thane K, Voth R, Klee R, Warnken T, Chukwu V, Frank N.Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are promising treatments to manage hyperinsulinemia in horses with insulin dysregulation (ID). Objective: The SGLT2i velagliflozin decreases insulin concentration in horses with ID. Methods: Privately-owned adult horses (n = 37) with laboratory-confirmed ID (low-dose oral sugar test insulin concentration > 75 μIU/mL). Methods: Double-blind randomized placebo-controlled trial. Horses received placebo (n = 19) or velagliflozin 0.3 mg/kg PO q24h (n = 18) for 20 weeks (Study Period 1, SP1) immediately followed by a 20-week ope...
Menzies-Gow NJ.Pituitary pars intermedia dysfunction (PPID) is a common, slowly progressive, neurodegenerative disorder of the older horse. Oxidative damage to the hypothalamic periventricular neurons results in loss of dopaminergic inhibition of the pars intermedia region of the pituitary gland. Consequently, there is increased production of the pro-opiomelanocortin (POMC)-derived hormones normally produced by this region, as well as initial melanocyte hypertrophy and hyperplasia, followed by adenomatous change. Clinical signs that are highly suggestive of the disease are generalised and regional hypertrich...
Scoggin KE, Adlan F, Fedorka CE, Rakha SI, Stout TAE, Troedsson MHT, Ali HE.The insulin-like growth factor (IGF) system regulates implantation, placental development, and angiogenesis in eutherian mammals. However, little is known about the changes in this system in equine placenta (chorioallantois; CA) and the endometrium (EN) during pregnancy, or the relationship to vascular endothelial growth factor () expression. The current study investigated the expression of the IGF system components, namely the ligands ( and ), their receptors (, , and ), and their binding proteins ( and s) in equine CA at 45 days, 4, 6, 10, and 11 months of gestational age (GA) and immediatel...
Michanek P, Bröjer J, Lilliehöök I, Fjordbakk C, Erkas M, Löwgren M, Hedeland M, Bergquist J, Ekstrand C.Sodium-glucose co-transporter 2 inhibitors like canagliflozin (CFZ) have shown promise in preventing hyperinsulinemia-associated laminitis in horses, but data on pharmacokinetics, tolerability, and controlled studies are limited. This randomized, open-label, placebo-controlled, crossover study evaluated these aspects of CFZ treatment in eight healthy Standardbred mares. Each horse received single supratherapeutic oral doses of CFZ (1.8 mg/kg or 3.6 mg/kg) and placebo, with a two-week washout between treatments. A graded glucose infusion (GGI) was administered post-treatment to evaluate glu...
Rey-Conejo R, Toribio RE, Möller S, Müller E, Fores-Jackson P.Insulin dysregulation is a key component of equine metabolic syndrome and is commonly assessed using basal insulin concentrations. Different analyzers may yield variable insulin results, limiting comparability. Objective: To assess the analytical performance of the ADVIA Centaur XPT chemiluminescent immunoassay (CLIA) for equine insulin measurement and to establish adapted decision thresholds based on comparison with a previously used CLIA method. Methods: Precision, linearity, and dilution recovery were assessed for the ADVIA Centaur XPT. A total of 89 equine serum samples submitted for basal...
Lowndes CR, Boyle AG, Kulp J, Stefanovski D, Davis JL, van Eps A.To characterize the effects of pioglitazone (2 mg/kg, PO, either q 24 h [PIO-SID] or q 12 h [PIO-BID]) in equids with severe hyperinsulinemia. Unassigned: 17 client-owned equids with severe resting hyperinsulinemia (> 100 µIU/mL) were assigned to PIO-SID or PIO-BID in a prospective cohort study with rolling enrollment over an 11-month study period (December 13, 2022, to November 17, 2023). Basal insulin, total and high-molecular-weight adiponectin concentrations, and plasma pioglitazone concentrations were measured over 70 days. Oral sugar tests (OSTs) were performed on days 0 and 28. Results...
McGuire CJ, Knowles EJ, Harris PA, Menzies-Gow NJ.Circulating insulin concentrations are used to quantify risk of laminitis in currently non-laminitic ponies. Basal serum activin A (AA) concentration has previously been positively correlated with serum insulin concentrations 60 minutes (T60) following an oral sugar test (OST) in ponies with equine metabolic syndrome. Therefore, circulating AA might be a useful marker for insulin dysregulation (ID) and laminitis risk. Objective: To explore the relationship between circulating AA concentrations at baseline (T0) and T60 in ponies that developed laminitis within six months and non-laminitic ponie...
Espinosa-López EM, Ortiz-Guisado B, Diez de Castro E, Durham A, Aguilera-Tejero E, Gómez-Baena G.Equine Metabolic Syndrome (EMS) is a multifactorial endocrine disorder characterized by obesity, insulin dysregulation (ID), and an increase in the risk of laminitis, a painful condition that can lead to euthanasia in severe cases. Diagnosing EMS is challenging and often relies on clinical history including obesity, difficulty in losing weight, and recurring episodes of laminitis. The gold standard for laboratory support of an EMS diagnosis is the identification of ID, with basal insulin being the simplest and most accessible method, especially in a field setting. However, various factors such...
Jantunen N, Raekallio M, Obrochta B, Tapio H, Gracia Calvo L, Rivera Pöyhönen R, Hagman K, Karikoski N.To assess the effects of a 4 hour detomidine constant rate infusion (CRI) with and without a vatinoxan CRI on energy metabolism and urine composition. Methods: Randomized, blinded, crossover study. Methods: Eight Finnhorses, 587 (550-620) kg [median (range)] and 13 (4-16) years old. Methods: Horses were administered an intravenous (IV) detomidine loading dose (0.01 mg kg) followed by 240 minutes CRI (0.015 mg kg hour) (DET) and the same detomidine protocol combined with an IV vatinoxan loading dose (0.15 mg kg) and CRI (0.05 mg kg hour) (DET+VAT). Blood samples for glucose, insulin, non-esteri...
Kerley BS, Harris P, Jacquay E, Askins M, McClendon M, Adams AA.Feeding small meals (∼1 g/kg BW DM basis) providing >10% nonstructural carbohydrates (NSC; starch + water soluble carbohydrate; WSC) has resulted in an augmented insulin response (AIR) in insulin dysregulated (ID) horses, but it's unclear if AIR reflects NSC content or the g NSC/kg BW/meal. Objective: The insulinemic responses of ID (n = 7) and non-insulin dysregulated (NID; n = 8) horses fed four feeds (A = 6.8% NSC; B = 14.9% NSC; C = 35.5% NSC; D = 44.6% NSC) at three levels of NSC intake (0.06, 0.11-0.12 and 0.17-0.18 g/kg BW) were evaluated in a randomized Latin square design across two...
Dosi M, Scott L, Payne H, Poldy J, Keen J, McGorum B, Malbon A, Morgan R.Hyperinsulinaemia (HI) is an important feature of Equine Metabolic Syndrome (EMS). It has been suggested that reduced hepatic clearance of insulin contributes to HI, particularly in humans affected by metabolic dysfunction-associated steatotic liver disease (MASLD). Objective: In obese horses with HI, insulin clearance is impaired and associated with MASLD. Methods: Tissue samples were collected at post-mortem from clinically well-characterized horses with HI (n = 13; basal insulin > 20 mIU/l) and without HI (control; n = 20). Methods: Retrospective observational study. Molecular d...
Davis EL, Wood AD, Potier JFN.Prevalence of endocrine disease in sport horses has been sparsely reported. They often compete well into their teenage years; thus, diagnosis and control of endocrine disease could be important to maintain performance and optimise health and welfare. The aim was to compare the prevalence of pituitary pars intermedia dysfunction (PPID), insulin dysregulation (ID) and metabolic obesity between sport and non-sport type breeds and assess disease progression. Blood samples submitted for plasma adrenocorticotropic hormone (ACTH), serum insulin or adiponectin were included in this study. Horses were ...
Fortier LA, Mohammed HO, Lust G, Nixon AJ.Composites of chondrocytes and polymerised fibrin were supplemented with insulin-like growth factor-I (IGF-I) during the arthroscopic repair of full-thickness cartilage defects in a model of extensive loss of cartilage in horses. Repairs facilitated with IGF-I and chondrocyte-fibrin composites, or control defects treated with chondrocyte-fibrin composites alone, were compared before death by the clinical appearance and repeated analysis of synovial fluid, and at termination eight months after surgery by tissue morphology, collagen typing, and biochemical assays. The structure of cartilage was ...
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 ...
Carter RA, Geor RJ, Burton Staniar W, Cubitt TA, Harris PA.This study described a scoring system for the assessment of apparent neck adiposity and evaluated morphometric measurements for assessment of neck and overall adiposity. Twenty-one barren Thoroughbred mares, 13 Arabian geldings and 75 Welsh, Dartmoor, or crossbred pony mares, were clinically examined and blood samples analysed for insulin, glucose, leptin, and triglycerides. Bodyweight (BW), height, length, girth and abdominal circumferences, neck length, neck crest height and neck circumference were measured, and body condition scores (BCS) and cresty neck scores (CNS) were rated. Girth:heigh...
Schnabel LV, Lynch ME, van der Meulen MC, Yeager AE, Kornatowski MA, Nixon AJ.Tendinitis remains a catastrophic injury among athletes. Mesenchymal stem cells (MSCs) have recently been investigated for use in the treatment of tendinitis. Previous work has demonstrated the value of insulin-like growth factor-I (IGF-I) to stimulate cellular proliferation and tendon fiber deposition in the core lesion of tendinitis. This study examined the effects of MSCs, as well as IGF-I gene-enhanced MSCs (AdIGF-MSCs) on tendon healing in vivo. Collagenase-induced bilateral tendinitis lesions were created in equine flexor digitorum superficialis tendons (SDFT). Tendons were treated with ...
Asplin KE, Sillence MN, Pollitt CC, McGowan CM.The purpose of this study was to determine the effects of prolonged administration of insulin, whilst maintaining normal glucose concentrations, on hoof lamellar integrity in vivo on healthy ponies with no known history of laminitis or insulin resistance. Nine clinically healthy, unrelated ponies were randomly allocated to either a treatment group (n =5; 5.9+/-1.7 years) or control group (n =4; 7.0+/-2.8 years). The treatment group received insulin via a euglycaemic hyperinsulinaemic clamp technique modified and prolonged for up to 72 h. Control ponies were infused with an equivalent volume of...
Frank N, Tadros EM.Abnormalities of insulin metabolism include hyperinsulinaemia and insulin resistance, and these problems are collectively referred to as insulin dysregulation in this review. Insulin dysregulation is a key component of equine metabolic syndrome: a collection of endocrine and metabolic abnormalities associated with the development of laminitis in horses, ponies and donkeys. Insulin dysregulation can also accompany prematurity and systemic illness in foals. Causes of insulin resistance are discussed, including pathological conditions of obesity, systemic inflammation and pituitary pars intermedi...
de Laat MA, McGowan CM, Sillence MN, Pollitt CC.Hyperinsulinaemia is known to induce laminitis experimentally in healthy ponies with no history of the condition. Horses are more insulin sensitive than ponies and whether prolonged hyperinsulinaemia and euglycaemia would have a similar laminitogenic effect requires study. Objective: To determine if laminitis results when the prolonged euglycaemic hyperinsulinaemic clamp technique (p-EHC) is applied to clinically normal Standardbred horses, and to monitor hoof wall temperature seeking an association between vascular activity and laminitis development. Methods: Eight young, clinically normal St...
Marycz K, Kornicka K, Basinska K, Czyrek A.Currently, equine metabolic syndrome (EMS), an endocrine disease linked to insulin resistance, affects an increasing number of horses. However, little is known about the effect of EMS on mesenchymal stem cells that reside in adipose tissue (ASC). Thus it is crucial to evaluate the viability and growth kinetics of these cells, particularly in terms of their application in regenerative medicine. In this study, we investigated the proliferative capacity, morphological features, and accumulation of oxidative stress factors in mesenchymal stem cells isolated from healthy animals (ASCN) and horses s...
Treiber KH, Kronfeld DS, Hess TM, Byrd BM, Splan RK, Staniar WB.To evaluate genetic and metabolic predispositions and nutritional risk factors for development of pasture-associated laminitis in ponies. Methods: Observational cohort study. Methods: 160 ponies. Methods: A previous diagnosis of laminitis was used to differentiate 54 ponies (PL group) from 106 nonlaminitic ponies (NL group). Pedigree analysis was used to determine a mode of inheritance for ponies with a previous diagnosis of laminitis. In early March, ponies were weighed and scored for body condition and basal venous blood samples were obtained. Plasma was analyzed for glucose, insulin, trigly...
Carter RA, Treiber KH, Geor RJ, Douglass L, Harris PA.The ability to predict ponies at increased risk of laminitic episodes, when exposed to nutrient dense pasture, would facilitate management to avoid disease. Objective: To identify variables and clinically useful cut-off values with reproducible diagnostic accuracy for the prediction of ponies that subsequently developed laminitis when exposed to nutrient dense pasture. Methods: A cohort of predominantly Welsh and Dartmoor ponies from a closed herd was evaluated in March 2006 (n = 74) and March 2007 (n = 57). Ponies were categorised as never laminitic or previously laminitic according to report...
Vick MM, Adams AA, Murphy BA, Sessions DR, Horohov DW, Cook RF, Shelton BJ, Fitzgerald BP.Recent studies associate obesity and insulin resistance in horses with development of abnormal reproductive function and debilitating laminitis. The factors contributing to insulin resistance in obese horses are unknown. However, human studies provide evidence that elevated inflammatory cytokines such as tumor necrosis factor alpha (TNFalpha), IL1, and IL6 play direct roles in development of obesity-associated insulin resistance. Thus, inflammation may be a key link between obesity and insulin resistance in horses. The aim of the current investigation was to examine possible relationships betw...
Dahlgren LA, van der Meulen MC, Bertram JE, Starrak GS, Nixon AJ.Flexor tendinitis is a common and debilitating injury of elite and recreational athletes. Healing may be improved through intratendinous injection of insulin-like growth factor-I (IGF-I), which has been shown in vitro to stimulate mitogenesis and enhance tendon matrix production. This study investigated the effects of intratendinous injection of IGF-I on tendon healing in an equine model of flexor tendinitis. Collagenase-induced lesions were created in the tensile region of theflexor digitorum superficialis tendon of both forelimbs of eight horses. Treated tendons were injected with 2 microg r...
de Laat MA, McGree JM, Sillence MN.Compared with some other species, insulin dysregulation in equids is poorly understood. However, hyperinsulinemia causes laminitis, a significant and often lethal disease affecting the pedal bone/hoof wall attachment site. Until recently, hyperinsulinemia has been considered a counterregulatory response to insulin resistance (IR), but there is growing evidence to support a gastrointestinal etiology. Incretin hormones released from the proximal intestine, glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide, augment insulin secretion in several species but require invest...
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...
Karikoski NP, Horn I, McGowan TW, McGowan CM.Endocrinopathic causes of laminitis may be a common underlying causative pathogenesis in first-opinion or field cases presenting with laminitis, as opposed to laminitis produced in inflammatory research models. This study aimed to determine whether evidence of an underlying endocrinopathy was present in horses presented for laminitis to a first-opinion/referral veterinary teaching hospital. A second aim was to compare the signalment of horses and ponies with laminitis with the equine hospital population during the same period. All horses presenting for laminitis at Helsinki University Equine T...
Frank N.The concept of an equine metabolic syndrome (EMS) was first proposed in 2002. This concept has developed over time, and EMS was recently described in a consensus statement released by the American College of Veterinary Internal Medicine. In human medicine, metabolic syndrome (MetS) refers to a set of risk factors that predict the risk of cardiovascular disease, including obesity, glucose intolerance and insulin resistance (IR), dyslipidemia, microalbuminuria, and hypertension. EMS shares some of the features of MetS, including increased adiposity, hyperinsulinemia, IR, but differs in that lami...
Marycz K, Kornicka K, Grzesiak J, Śmieszek A, Szłapka J.Equine metabolic syndrome (EMS) is mainly characterized by insulin resistance, obesity, and local or systemic inflammation. That unfriendly environment of adipose tissue has huge impact on stem cells population (ASC) residing within. In the present study, using molecular biology techniques and multiple imaging techniques (SEM, FIB-SEM, and confocal microscopy), we evaluated the impact of EMS on ASC viability and chondrogenic differentiation. Moreover, we visualized the mitochondrial network and dynamics in ASC and ASC during control and chondrogenic conditions. In control conditions, ASC were ...
Marycz K, Kornicka K, Szlapka-Kosarzewska J, Weiss C.Nowadays, endocrine disorders have become more frequent in both human and veterinary medicine. In horses, reduced physical activity combined with carbohydrate and sugar overload may result in the development of the so-called equine metabolic syndrome (EMS). EMS is characterized by insulin resistance, hyperinsulinemia, elevated blood triglyceride concentrations and usually obesity. Although the phenotypic features of EMS individuals are well known, the molecular mechanism underlying disease development remains elusive. Therefore, in the present study, we analyzed insulin-sensitive tissues, i.e....
Bamford NJ, Potter SJ, Harris PA, Bailey SR.Breed-related differences may occur in the innate insulin sensitivity (SI) of horses and ponies, an important factor believed to be associated with the risk of laminitis. The aim of this study was to measure the glucose and insulin responses of different breeds of horses and ponies in moderate body condition to a glucose-containing meal and to compare these responses with the indices of SI as determined by a frequently sampled intravenous glucose tolerance test (FSIGT). Eight Standardbred horses, 8 mixed-breed ponies, and 7 Andalusian-cross horses with a mean ± SEM BCS 5.0 ± 0.3 of 9 were us...
Frank N, Elliott SB, Brandt LE, Keisler DH.To compare obese horses with insulin resistance (IR) with nonobese horses and determine whether blood resting glucose, insulin, leptin, and lipid concentrations differed between groups and were correlated with combined glucose-insulin test (CGIT) results. Methods: 7 obese adult horses with IR (OB-IR group) and 5 nonobese mares. Methods: Physical measurements were taken, and blood samples were collected after horses had acclimated to the hospital for 3 days. Response to insulin was assessed by use of the CGIT, and maintenance of plasma glucose concentrations greater than the preinjection value ...
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...
Menzies-Gow NJ, Harris PA, Elliott J.Certain individuals appear to be predisposed to recurrent pasture-associated laminitis. Previous studies have predominantly investigated risk factors only after disease occurrence. Objective: To investigate risk factors for pasture-associated laminitis prior to disease occurrence. Methods: Prospective cohort study. Methods: Non-laminitic ponies aged ≥7 years were recruited. Body condition score (BCS), height, weight, crest height and thickness were measured and an overnight dexamethasone suppression test performed. Plasma or serum adiponectin, leptin, triglyceride, basal insulin, insulin pos...
Karikoski NP, McGowan CM, Singer ER, Asplin KE, Tulamo RM, Patterson-Kane JC.Laminitis in equids is a clinical syndrome usually associated with systemic disease. Endocrinopathies recently have been recognized as the most common cause of laminitis, with hyperinsulinemia playing a key role. Descriptions of laminitis-associated lesions have been confusing due to the wide range of experimental models used, failure of adequate clinical documentation for naturally occurring cases, lack of separate analysis of inflammatory and endocrinopathic laminitis, and uncertainty regarding normal morphological variation of lamellae. In this study, lamellar morphology and pathology were ...
Bailey SR, Habershon-Butcher JL, Ransom KJ, Elliott J, Menzies-Gow NJ.To determine the metabolic phenotype of a group of laminitis-prone ponies when at pasture in summer, compared with when at pasture in winter. Methods: 40 ponies of various breeds predisposed to recurrent pasture-associated laminitis and 40 unaffected control ponies. Methods: Body condition score and size of the crest of the neck were assessed, blood samples obtained, and blood pressure measured by use of an indirect oscillometric technique, while ponies were kept on winter pasture (last week of November or beginning of December) and again on summer pasture (June). Serum insulin concentration a...
Hoffman RM, Boston RC, Stefanovski D, Kronfeld DS, Harris PA.Insulin resistance is considered a risk factor in obesity, laminitis, exertional rhabdomyolysis, and osteochondrosis. The objective was to use the minimal model to estimate glucose effectiveness (Sg) and insulin sensitivity (Si) in nonobese to obese horses initially adapted to forage only, then adapted to forage plus supplements rich in starch and sugar (SS) or fiber and fat (FF). Ten Thoroughbred geldings, with BCS of 5 (nonobese), 6 (moderately obese), and 7 to 8 (obese), were adapted to pasture and hay, allocated to two groups, and fed SS or FF in a switch-back design with 8 wk of adaptatio...
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...
Vézina Audette R, Lavoie-Lamoureux A, Lavoie JP, Laverty S.Osteoarthritis (OA) is a degenerative disease of joint tissues that causes articular cartilage erosion, osteophytosis and loss of function due to pain. Inflammation and inflammatory cytokines in synovial fluid (SF) contribute to OA progression. Intra-articular (IA) injections of multipotent mesenchymal stromal cells (MSCs) are employed to treat OA in both humans and animals. MSCs secrete paracrine pro-inflammatory and anabolic signaling molecules that promote tissue repair. The objective of this study was to investigate the effects of OASF on the gene expression of paracrine signaling molecule...
Bertin FR, de Laat MA.Insulin dysregulation is the hallmark of equine metabolic syndrome and has received attention because of its direct association with laminitis. In the absence of an adequate treatment for laminitis, a focus on prophylaxis is needed, making early detection of individuals at risk of developing laminitis one of the main challenges in equine endocrinology. Recent studies have shown that insulin dysregulation goes beyond tissue insulin resistance and it is now demonstrated that the equine enteroinsular axis plays a major role in insulin secretion and equine hyperinsulinaemia. In this review, we dis...
Johnson PJ.Certain management practices tend to promote the development of obesity (metabolic syndrome) in mature horses as they enter their teenage years. These management practices include the provision of starch-rich (high glycemic index) and fat-supplemented rations to healthy horses that are relatively inactive. Some horse breeds and ponies appear to be genetically predisposed to metabolic syndrome. The accretion of intra-abdominal adiposity by equids is associated with the development of insulin insensitivity (hyperinsulinemia), glucose intolerance, dyslipidemia, hypertension, and insidious-onset l...
Nawrocka D, Kornicka K, Śmieszek A, Marycz K.Equine Metabolic Syndrome (EMS) is a steadily growing life-threatening endocrine disorder linked to insulin resistance, oxidative stress, and systemic inflammation. Inflammatory microenvironment of adipose tissue constitutes the direct tissue milieu for various cell populations, including adipose-derived mesenchymal stromal cells (ASCs), widely considered as a potential therapeutic cell source in the course of the treatment of metabolic disorders. Moreover, elevated oxidative stress induces inflammation in intestinal epithelial cells (IECs)-the first-line cells exposed to dietary compounds. In...
