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.
Bourebaba L, Kępska M, Qasem B, Zyzak M, Łyczko J, Klemens M, Mularczyk M, Marycz K.Equine metabolic syndrome (EMS) is a steadily growing endocrine disorder representing a real challenge in veterinary practice. As a multifactorial condition, EMS is characterized by three main metabolic abnormalities including insulin resistance, increased adiposity or obesity and hoof laminitis. Adipose tissue dysfunction is recognized as a core pathophysiological determinant of EMS, as it strongly participates to lipotoxicity and systemic metaflammation, both of which have been closely linked to the development of generalized insulin resistance. Besides, sex hormone binding globulin (SHBG) i...
de Laat MA, Fitzgerald DM, Harris PA, Bailey SR.High plasma concentrations of insulin can cause acute laminitis. Ponies and horses with insulin dysregulation (ID) exhibit marked hyperinsulinemia in response to dietary hydrolyzable carbohydrates. Glucagon-like peptide-1 (GLP-1), an incretin hormone released from the gastrointestinal tract, enhances insulin release, and is increased postprandially in ponies with ID. The aim of this study was to determine whether blocking the GLP-1 receptor reduces the insulin response to a high glycemic meal. Five adult ponies were adapted to a cereal meal and then given two feed challenges 24 h apart of a me...
Robles M, Rousseau-Ralliard D, Dubois C, Josse T, Nouveau É, Dahirel M, Wimel L, Couturier-Tarrade A, Chavatte-Palmer P.In horses, the prevalence of obesity is high and associated with serious metabolic pathologies. Being a broodmare has been identified as a risk factor for obesity. In other species, maternal obesity is known to affect the development of the offspring. This article is a follow-up study of previous work showing that Obese mares (O, n = 10, body condition score > 4.25 at insemination) were more insulin resistant and presented increased systemic inflammation during pregnancy compared to Normal mares (N, n = 14, body condition score < 4 at insemination). Foals born to O mares were more insulin-resi...
Al-Ansari AS, Golding E, Walshe N, Mooney CT, Duggan V.Equine obesity combined with insulin dysregulation (ID) is a major risk factor associated with laminitis. Some pony breeds appear to be at increased risk. However, little is known regarding the prevalence of obesity or hyperinsulinaemia as evidence of ID in Irish ponies. Objective: To investigate the prevalence of obesity and associated endocrine/metabolic disease conditions in Connemara ponies and to determine if hyperinsulinaemia in these ponies could be predicted by morphometric or metabolic markers. Methods: Cross-sectional study. Methods: The study population included registered Connemara...
Hallman I, Tapio H, Raekallio M, Karikoski N.To assess the effects of an α-adrenoceptor agonist (detomidine) constant rate infusion (CRI) with and without an α-adrenoceptor antagonist (vatinoxan) CRI on blood insulin and glucose concentrations, heart rate, intestinal borborygmi, and sedation during and after infusion in horses. Methods: Randomized, blinded, crossover, experimental study. Methods: A total of nine healthy, adult Finnhorse mares. Methods: Horses were treated with an intravenous (IV) detomidine loading dose (0.01 mg kg), followed by CRI (0.015 mg kg hour), and the same doses of detomidine combined with an IV vatinoxan load...
Barnabé MA, Elliott J, Harris PA, Menzies-Gow NJ.The hormones insulin and adiponectin are commonly measured in equids because of their involvement in endocrinopathic laminitis. These are currently measured in serum/plasma, although jugular venipuncture can cause stress in some animals and may be impossible in needle-shy individuals. However, both hormones can be measured in saliva in other species. Objective: To determine whether [insulin] and [total adiponectin] are detectable in equine saliva using automated assays and whether saliva collection is associated with changes in stress indicators. Additionally, the correlation between serum and...
Frers F, Delarocque J, Feige K, Huber K, Warnken T.The underlying molecular mechanisms leading to insulin dysregulation are poorly understood in horses. Therefore, this study aimed to determine if insulin dysregulation is associated with an altered basal expression and extent of phosphorylation of key proteins of the insulin signaling cascade in liver (LT), muscle (MT), and subcutaneous adipose tissue (AT) under basal and stimulated conditions. Twelve Icelandic horses were subjected (1) to an oral glucose (Gluc PO) challenge and (2) to an intravenous (Ins IV) insulin challenge in a crossover study. Biopsies of LT, MT, and AT were taken in vivo...
Lindåse S, Nostell K, Forslund A, Bergsten P, Bröjer J.Decreasing hyperinsulinemia is crucial in preventing laminitis in insulin dysregulated (ID) horses. Complementary pharmacological treatments that efficiently decrease postprandial hyperinsulinemia in ID horses are needed. Objective: Compare short-term effects of canagliflozin vs placebo on glucose and insulin responses to an oral sugar test (OST) as well as the effects on body weight and triglyceride concentrations in horses with ID. Methods: Sixteen privately-owned ID horses. Methods: A single-center, randomized, double-blind, placebo-controlled, parallel design study. The horses were randomi...
Fitzgerald DM, Cash CM, Dudley KJ, Sibthorpe PEM, Sillence MN, de Laat MA.Active glucagon-like peptide-1 (aGLP-1) has been implicated in the pathogenesis of equine insulin dysregulation (ID), but its role is unclear. Cleavage of proglucagon (coded by the GCG gene) produces aGLP-1 in enteral L cells. Objective: The aim in vivo was to examine the sequence of the exons of GCG in horses with and without ID, where aGLP-1 was higher in the group with ID. The aims in vitro were to identify and quantify the expression of GCG in the equine intestine (as a marker of L cells) and determine intestinal secretion of aGLP-1. Methods: Genomic studies were case-control studies. Expr...
Heimann M, Elashry MI, Klymiuk MC, Eldaey A, Wenisch S, Arnhold S.The investigation of adipose tissue-derived mesenchymal stem cells (ASCs) has received considerable interest in regenerative medicine. A nontoxic adipogenic induction protocol valid for cells of different mammalian species has not been described. This study aims to establish an adipogenic differentiation protocol suitable for horses, sheep, dogs, murines, and human cells. An optimized rosiglitazone protocol, consisting of 5% fetal calf serum in Dulbecco's Modified Eagle's Medium, 10 μg/mL insulin, 0.55 μg/mL transferrin, 6.8 ng sodium selenite, 1 μM dexamethasone, and 1-5 μM of rosiglitazo...
Ward AB, Harris PA, Argo CM, Watson CA, Burns NM, Neacsu M, Russell WR, Grove-White D, Morrison PK.Native ponies are at increased risk of obesity and metabolic perturbations, such as insulin dysregulation (ID), a key risk factor for endocrinopathic laminitis. Management and feeding practices can be adapted to maintain healthy body condition and support metabolic health, but owners may inadvertently provide their ponies with inappropriate management leading to obesity and exacerbating risk of metabolic disease. Adoption of preventative weight management approaches (WMAs), including regular monitoring of body condition, providing appropriate preserved forage, promoting seasonal weight loss, a...
Barnabé MA, Elliott J, Harris PA, Menzies-Gow NJ.Hypoadiponectinaemia is a risk factor for endocrinopathic laminitis, but the directionality and nature of its association with insulin dysregulation is unclear. Objective: To investigate the effects of short-term induced hyperinsulinaemia and dexamethasone challenge on circulating [total adiponectin] and whole blood expression of adiponectin (AdipoR1 and AdipoR2), insulin, and insulin-like growth factor 1 (IGF-1) receptors in insulin-sensitive ponies. Methods: In vivo experiment. Methods: Six never-laminitic, insulin-sensitive, native-breed UK ponies first underwent a dexamethasone challenge (...
Barnabé MA, Elliott J, Harris PA, Menzies-Gow NJ.Equine metabolic syndrome is a collection of risk factors associated with an increased risk of endocrinopathic laminitis. All affected animals display insulin dysregulation and some may show adiponectin dysregulation and/or excessive adiposity. However, the relationship between obesity and hypoadiponectinaemia in equids remains unclear. Objective: To investigate the relationship between obesity and circulating plasma total adiponectin (TA) concentrations in native-breed ponies in England. Methods: Secondary data analysis. Methods: Data collected for three previous studies were retrospectively ...
Bourebaba L, Serwotka-Suszczak A, Bourebaba N, Zyzak M, Marycz K.Hyperactivation of protein tyrosine phosphatase (PTP1B) has been associated with several metabolic malfunctions ranging from insulin resistance, metaflammation, lipotoxicity, and hyperglycaemia. Liver metabolism failure has been proposed as a core element in underlying endocrine disorders through persistent inflammation and highly fibrotic phenotype. Unassigned: In this study, the outcomes of PTP1B inhibition using trodusquemine (MSI-1436) on key equine metabolic syndrome (EMS)-related alterations including inflammation, fibrosis, and glucose uptake have been analyzed in liver explants collect...
de Laat MA, Sillence MN.Blood glucose concentration is often measured during an oral glucose test (OGT), but is not thought to aid in diagnosing insulin dysregulation (ID) or pituitary pars intermedia dysfunction (PPID). The aim of this retrospective study was to investigate whether the change in blood glucose concentration during an OGT aligned with indicators of equine metabolic syndrome or PPID, including serum insulin and plasma ACTH concentrations, clinical observations, age, sex, breed type and the test dose. The cohort included 149 horses, miniature horses, and ponies that had undergone an in-feed OGT and clin...
Boger BL, Manfredi JM, Loucks AR, Salamey MZ, Kapeller LE, Fricano AG, Winkler A, Yob C, Colbath AC.Corticosteroids are a commonly used, inexpensive intra-articular treatment for osteoarthritis which may increase the risk for laminitis in horses due, in part, to hyperinsulinaemia. Humans with metabolic syndrome experience increases in insulin and glucose concentrations post-injection, but responses in horses are unknown. Objective: To determine the effect of a single intra-articular (IA) dose of triamcinolone acetate (TA) on blood insulin and glucose concentrations. Methods: Before-after study. Methods: Ten horses with normal insulin regulation as assessed by an oral sugar test received 18...
Sibthorpe PEM, Fitzgerald DM, Sillence MN, de Laat MA.Gastrointestinal peptides, such as glucagon-like peptide-2 (GLP-2), could play a direct role in the development of equine hyperinsulinaemia. Objective: To describe the secretory pattern of endogenous GLP-2 over 24 h in healthy ponies and determine whether oral administration of a synthetic GLP-2 peptide increases blood glucose or insulin responses to feeding. Methods: A cohort study followed by a randomised, controlled, cross-over study. Methods: In the cohort study, blood samples were collected every 2 h for 24 h in seven healthy ponies and plasma [GLP-2] was measured. In the cross-over...
Bourebaba N, Sikora M, Qasem B, Bourebaba L, Marycz K.Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade inflammation and predisposition to laminitis is a critical endocrine disorder among the most prevalent conditions affecting horses from different breeds. According to the most recent research, low human sex hormone-binding globulin (SHBG) serum levels correlate with an increased risk of obesity, insulin resistance and diabetes, and may contribute to overall metabolic dysregulations. This study aimed to test whether exogenous SHBG could protect EMS affected adipose-derived stromal stem cells (EqASC) from apoptosis,...
Delarocque J, Feige K, Carslake HB, Durham AE, Fey K, Warnken T.The measurement of the blood insulin concentration, and comparison to cut-offs, is essential in diagnosing insulin dysregulation, a common equine endocrinopathy. However, different insulin assays provide disparate results. We aimed to ease comparison between assays by compiling original and published data into a web app to convert insulin measurements from one assay to another. Data were available for ADVIA Centaur insulin chemiluminescent immunoassay (CLIA), Beckman Coulter insulin radioimmunoassay (RIA), Immulite 1000 CLIA, Immulite 2000 CLIA, Immulite 2000 XPi CLIA, Mercodia equine insulin ...
Knowles EJ, Harris PA, Elliott J, Chang YM, Menzies-Gow NJ.Serum insulin concentration at 60 min (InsulinT60) during an oral sugar test (OST) indicates future laminitis risk and insulin dysregulation (ID). Associations between InsulinT60 and physical and owner-reported variables may help clinicians select individuals for ID testing. Associations between InsulinT60 and other metabolic markers may help elucidate ID pathophysiology. Objective: To describe associations between (A) season, physically-apparent and owner-reported factors and binary InsulinT60 interpretation (initial models) and (B) variables included in the initial models, other metabolic ...
Myćka G, Ropka-Molik K, Cywińska A, Szmatoła T, Stefaniuk-Szmukier M.Recent studies have shown that in Arabian horse muscle, long-term exercise-induced expression of genes related to fatty acid degradation and the downregulation of genes belonging to the glycolysis/gluconeogenesis and insulin signalling pathways. Long-lasting physical exertion may trigger the metabolism to switch the main energy source from carbohydrates to lipids due to higher caloric content. Objective: To describe the metabolism adaptation at the whole transcriptome of blood to endurance effort in Arabian horses. Methods: In vivo experiment. Methods: Venous blood samples from 10 Arabian hors...
Colmer SF, Adams AA, Adam E, Miller R, Stefanovski D, Kulp JC, van Eps A.A single dose of metformin administered 1 h prior to oral glucose challenge was previously shown to reduce insulinaemic responses in horses with experimentally-induced insulin dysregulation (ID). Targeted administration could be useful for controlling post-prandial hyperinsulinaemia in horses with naturally-occurring ID.
Clark BL, Stewart AJ, Kemp KL, Bamford NJ, Bertin FR.Field tests and their association with laminitis have not been evaluated in large cohorts. The objectives of this study were to evaluate the performance of basal insulin (BI), the oral sugar test (OST) and the insulin tolerance test (ITT) to diagnose ID and investigate their association with laminitis. Insulin dysregulation status was determined in 146 ponies using BI (insulin concentration >20 µIU/mL), an OST (insulin concentration >65 µIU/mL at 60 or 90min after oral administration of 0.45mL/kg corn syrup) and an ITT (< 50% reduction in glucose concentration 30min after intravenous adminis...
Stefaniuk-Szmukier M, Piórkowska K, Ropka-Molik K.Equine metabolic syndrome (EMS) has become an important issue in modern veterinary medicine and is linked to the common, extremely painful, most-of-the-time performance-terminating hoof laminitis. The growing knowledge in the field of genetic background, inducing environmental factors, diagnosis, treatment and maintenance of affected equines led us to summarise the available information to be used not only for scientific purposes but for fieldwork. In horses, the clinical presentation of EMS includes: obesity or local fat deposition, bilateral lameness or hoof rings attributed to ongoing or pr...
Bourebaba L, Zyzak M, Sikora M, Serwotka-Suszczak A, Mularczyk M, Al Naem M, Marycz K.Sex hormone binding globulin (SHBG) deteriorated expression has been recently strongly correlated to increased level of circulating pro-inflammatory cytokines and insulin resistance, which are typical manifestations of equine metabolic syndrome (EMS). Despite previous reports demonstrated the potential therapeutic application of SHBG for liver-related dysfunctions, whether SHBG might modulate equine adipose-derived stem/stromal cells (EqASCs) metabolic machinery remains unknown. Therefore, we evaluated for the first time the impact of SHBG protein on metabolic changes in ASCs isolated from hea...
Jacquay ET, Harris PA, Adams AA.Transportation of horses on short journeys can lead to an increase in stress. There are known age-associated changes in immune and metabolic responses in horses; however, no research exists evaluating how age may influence these responses to transportation stress. Eleven mares within two age groups, aged (n = 5, 22 ± 1 year) or young (n = 6, 2 ± 1 year), were transported 1 hour and 20 minutes. Peripheral blood and saliva were collected before and after transportation at baseline (2 to 3 weeks prior to transportation), 24 hours pre-transport, 1 hour before loading, 15 minutes, 30 minutes,...
Frers F, Delarocque J, Huber K, Feige K, Warnken T.Both, oral and intravenous (IV) testing protocols, are recommended and still used to detect insulin dysregulation (ID) in equids. However, IV tests mainly focus on peripheral insulin resistance (IR), while oral tests assess hyperinsulinemia (HI), which are different aspects of ID. The objective of this study was to describe if horses with HI also demonstrate IR and consequently can be detected by a modified 2-step insulin response test (2-step IRT) performed with a veterinary approved porcine zinc insulin (PZI). Twelve Icelandic horses were subjected to an OGT and 2-step IRT in a crossover stu...
Akinniyi OO, Sackey AKB, Ochube GE, Mshelia PW, Musa FA, Elijah MO, Jolayemi KO.Insulin dysregulation (ID) is central to the pathophysiology of equine metabolic syndrome (EMS), putting the horse at risk of laminitis. There is a paucity of information on the status of EMS in Nigeria. This study aimed to determine the occurrence of EMS, clinical manifestations, and associated risk factors in Nigeria. A cross-sectional study was carried out. Selected horses underwent an insulin 2-step response test to ascertain insulin dysregulation; a physical examination was carried out to diagnose laminitis and obesity. Risk factors were assessed using a questionnaire. The overall prevale...
McGowan CM, Ireland JL.Equine endocrine disease is an important area for equine research, requiring an appropriate case definition for inclusion and criteria for exclusion from disease. Defining a case for research may be different from criteria for clinical diagnosis. Further, clinical diagnosis recommendations have been changing regularly, making this area challenging for equine scientists. This review discusses the diagnosis of major equine endocrine diseases, pituitary pars intermedia dysfunction, equine metabolic syndrome and insulin dysregulation, focusing on the most appropriate diagnostic methods for researc...
Clark BL, Bamford NJ, Stewart AJ, McCue ME, Rendahl A, Bailey SR, Bertin FR, Norton EM.The HMGA2:c.83G>A variant was identified in Welsh ponies having pleiotropic effects on height and insulin concentration. Objective: Determine whether the HMGA2:c.83G>A variant is associated with decreased height and higher basal insulin concentrations across pony breeds. Methods: Two hundred thirty-six ponies across 6 breeds. Methods: Cross-sectional study. Ponies were genotyped for the HMGA2:c.83G>A variant and phenotyped for height and basal insulin concentrations. Stepwise regression was performed for model analysis using a linear regression model for height and mixed linear model ...
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 ...
Treiber KH, Kronfeld DS, Hess TM, Boston RC, Harris PA.To develop proxies calculated from basal plasma glucose and insulin concentrations that predict insulin sensitivity (SI; L.min(-1) x mU(-1)) and beta-cell responsiveness (ie, acute insulin response to glucose [AIRg]; mU/L x min(-1)) and to determine reference quintiles for these and minimal model variables. Methods: 1 laminitic pony and 46 healthy horses. Methods: Basal plasma glucose (mg/dL) and insulin (mU/L) concentrations were determined from blood samples obtained between 8:00 AM and 9:00 AM. Minimal model results for 46 horses were compared by equivalence testing with proxies for screeni...
Johnson PJ, Wiedmeyer CE, LaCarrubba A, Ganjam VK, Messer NT.Although much has been written about laminitis in the context of its association with inflammatory processes, recognition is growing that most cases of laminitis examined by veterinarians in private practice are those associated with pasture grazing, obesity, and insulin resistance (IR). The term 'endocrinopathic laminitis' has been adopted to classify the instances of laminitis in which the origin seems to be more strongly associated with an underlying endocrinopathy, such as either IR or the influence of corticosteroids. Results of a recent study suggest that obesity and IR represent the mos...
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...
Vick MM, Murphy BA, Sessions DR, Reedy SE, Kennedy EL, Horohov DW, Cook RF, Fitzgerald BP.To determine whether an inflammatory challenge induces insulin resistance in horses and examine possible contributions of adipose tissue to inflammatory cytokine production. Methods: 15 adult mares. Methods: Lipopolysaccharide (0.045 mug/kg, IV) or saline solution was administered, and insulin sensitivity was determined by means of the hyperinsulinemic, euglycemic clamp procedure or an adipose tissue biopsy was performed. Adipose tissue samples were collected, and mature adipocytes were obtained. Mature adipocytes were stimulated with lipopolysaccharide or dedifferentiated into preadipocytes a...
McGowan CM, Dugdale AH, Pinchbeck GL, Argo CM.Few studies have examined the effect of dietary restriction in horses with equine metabolic syndrome (EMS). This study aimed to determine improvements in insulin sensitivity following dietary restriction for 6 weeks, and to determine if the improvement would be greater in horses receiving short-chain fructo-oligosaccharides (sc-FOS). Dietary management involved feeding grass hay, restricted to 1.25% of body mass (BM) as daily dry matter intake and soaked in cold water prior to feeding, with the addition of a vitamin and mineral nutraceutical supplement with or without the addition of sc-FOS (1...
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, ...
Rendle DI, Rutledge F, Hughes KJ, Heller J, Durham AE.Metformin is a potential therapeutic agent for the treatment of insulin resistance (IR). In laboratory animals, orally administered metformin reduces intestinal glucose absorption and may therefore affect insulinaemic responses to oral carbohydrate ingestion. Objective: To determine whether pretreatment with metformin reduces plasma glucose concentration and insulin responses following consumption of dextrose in horses. Methods: Therapeutic cross-over study. Methods: Seven healthy Standardbred and Thoroughbred geldings were subjected to an oral dextrose challenge test on 4 occasions: with and ...
Durham AE, Rendle DI, Newton JE.Laminitis in equids is a very common debilitating disease, and insulin resistance (IR) and hyperinsulinaemia are increasingly recognised as important predisposing factors. Pharmacological modification of IR and hyperinsulinaemia might reduce the risk of laminitis. Objective: Metformin, a drug commonly prescribed for treatment of human IR, may also decrease IR in equids. Methods: Eighteen horses and ponies with IR and recurrent laminitis were treated with 15 mg/kg bwt metformin per os q. 12 h. Each animal served as its own control by comparing pre- and post treatment proxies for IR, insulin sen...
Tiley HA, Geor RJ, McCutcheon LJ.To determine effects of dexamethasone on glucose dynamics and insulin sensitivity in healthy horses. Methods: 6 adult Standardbreds. Methods: In a balanced crossover study, horses received dexamethasone (0.08 mg/ kg, IV, q 48 h) or an equivalent volume of saline (0.9% NaCl) solution (control treatment) during a 21-day period. Horses underwent a 3-hour frequently sampled IV glucose tolerance test (FSIGT) 2 days after treatment. Minimal model analysis of glucose and insulin data from FSIGTs were used to estimate insulin sensitivity (Si), glucose effectiveness (Sg), acute insulin response to gluc...
Carslake HB, Pinchbeck GL, McGowan CM.The epidemiology of equine metabolic syndrome (EMS) is poorly described. Objective: To estimate the prevalence of EMS in native UK ponies and cobs in England and Wales and identify associated risk factors. Methods: Cross-sectional study. Methods: Breeders registered with UK native pony breed societies and registered riding schools and livery yards within a set radius were invited to participate. All native UK ponies and cobs aged 3-14 years and not diagnosed or being treated for conditions likely to affect insulin regulation at participating premises were eligible. Animals underwent a clinica...
Rapson JL, Schott HC, Nielsen BD, McCutcheon LJ, Harris PA, Geor RJ.Age and diet may affect insulin sensitivity (SI) but these factors have received limited investigation in horses. Objective: To measure minimal model parameters during an insulin-modified frequently sampled intravenous glucose tolerance test (FSIGTT) after adaptation to a forage only diet (HAY) or forage supplemented with either starch/sugar-rich (SS) or oil/fibre-rich (FF) concentrate feeds; and to assess glucose and insulin responses to a standardised meal challenge (SMC, 4 g/kg BW of SS) after diet adaptation in adult and aged mares. Methods: Latin square design with eight adult (5-12 yea...
Bailey SR, Menzies-Gow NJ, Harris PA, Habershon-Butcher JL, Crawford C, Berhane Y, Boston RC, Elliott J.To determine whether pasture, and specifically the addition of fructan carbohydrate to the diet, induces exaggerated changes in serum insulin concentration in laminitispredisposed (LP) ponies, compared with ponies with no history of the condition, and also to determine insulin responses to the dexamethasone suppression test. Methods: Prospective study. Methods: 10 LP and 11 control adult nonobese mixed-breed ponies. Methods: Insulin-modified IV glucose tolerance tests were performed (5 ponies/group). In diet studies, ponies were kept on pasture and then changed to a hay diet (10 ponies/group)....
de Laat MA, Reiche DB, Sillence MN, McGree JM.Endocrinopathic laminitis is common in horses and ponies, but the recurrence rate of the disease is poorly defined. Objective: To determine the incidence of, and risk factors for, the recurrence of endocrinopathic laminitis. Methods: Privately owned horses and ponies with acute laminitis (n = 317, of which 276 cases with endocrinopathic laminitis were followed up to study completion). Methods: This prospective cohort study collected data on veterinary-diagnosed cases of acute laminitis for 2 years. Each case was classified on acceptance to the study as endocrinopathic or non-endocrinopathi...
Treiber K, Carter R, Gay L, Williams C, Geor R.Inflammatory and redox signals could render lamellar tissue susceptible to damage and contribute to higher risk for laminitis in obese or insulin resistant ponies just as these factors contribute to health risks in humans with metabolic syndrome. This study evaluated circulating markers of inflammatory and redox status in ponies that had a history of recurrent bouts of pasture-associated laminitis (PL, n = 42) or had never developed clinical laminitis (NL, n = 34) under the current management conditions. There were no differences (P > 0.05) between PL and NL ponies for markers of antioxidan...
Pratt SE, Geor RJ, McCutcheon LJ.There is evidence that adaptation to diets rich in nonstructural carbohydrates (NSC) contributes to the development of insulin resistance in horses. To date, however, no study in horses has examined the effects of physical conditioning on diet-associated alterations in insulin sensitivity and glucose tolerance. Objective: To examine the effects of adaptation to concentrate feeds rich in NSC or fat on insulin sensitivity and glucose tolerance in horses, both in the sedentary state and after a subsequent period of physical conditioning. Methods: Fourteen mature Standardbred horses underwent both...
Tóth F, Frank N, Martin-Jiménez T, Elliott SB, Geor RJ, Boston RC.Hyperinsulinaemia is detected in horses with insulin resistance (IR) and has previously been attributed to increased pancreatic insulin secretion. Connecting peptide (C-peptide) can be measured to assess pancreatic function because it is secreted in equimolar amounts with insulin and does not undergo hepatic clearance. Objective: A human double antibody radioimmunoassay (RIA) detects C-peptide in equine serum and concentrations would reflect responses to different stimuli and conditions. Methods: A validation procedure was performed to assess the RIA. Six mature mares were selected and somatos...
Phillips T, Ferraz I, Bell S, Clegg PD, Carter SD, Mobasheri A.Glucose serves as the major energy substrate for articular chondrocytes and as the main precursor for the synthesis of extracellular matrix glycosaminoglycans in cartilage. Chondrocytes have been shown to express several glucose transporter (GLUT) isoforms including GLUT1 and GLUT3. The aim of this investigation was to determine the effects of endocrine and cytokine factors on the capacity of equine articular chondrocytes for transporting 2-deoxy-d-[2,6-3H] glucose and on the expression levels of GLUT1 and GLUT3. Chondrocytes maintained in monolayer culture were stimulated for 24 h with TNF-al...
Schröder HJ.The growth of the fetus is determined by substrate supply mostly for mass accretion and energy gain, and by control systems. Experiments with whole animal models will face the following problems: (1) The fetus, like a three compartmental "Russian doll", is at the end of a long supply chain. There are interactions (e.g. hormones) and partitioning of substrates between the compartments. (2) The fetal organism is growing and differentiating at the same time and not in a steady-state. Experimental results thus depend on gestational age. (3) About 75% of animal experiments on fetal growth restricti...
Goodrich LR, Brower-Toland BD, Warnick L, Robbins PD, Evans CH, Nixon AJ.Insulin-like growth factor-I (IGF-I) is one of the most influential growth factors in cartilage repair. Maintenance of adequate IGF-I levels after articular repair procedures is complicated by the short biological half-life of IGF-I in vivo. This study investigated the potential for more prolonged IGF-I delivery through direct adenoviral mediated transduction of synovial tissues in the metacarpophalangeal (MCP) joints of horses. The use of a large animal model provided a structurally similar and metabolically relevant corollary to the human knee. The complete IGF-I coding sequence was packaged...
Jacob SI, Geor RJ, Weber PSD, Harris PA, McCue ME.Diagnosis of equine pituitary pars intermedia dysfunction (PPID) remains a challenge as multiple factors (stress, exercise, and time of year) influence ACTH and cortisol concentrations. To assess endocrine status in a study designed to evaluate the effects of age and diet on glucose and insulin dynamics, we performed thyrotropin-releasing hormone (TRH) stimulation tests and overnight dexamethasone suppression tests in March, May, August, and October on 16 healthy Thoroughbred and Standardbred mares and geldings. Horses were grouped by age: adult (mean ± SD; 8.8 ± 2.9 yr; n = 8) and aged (20...
Burns TA, Watts MR, Weber PS, McCutcheon LJ, Geor RJ, Belknap JK.Hyperinsulinaemia has been implicated in the pathogenesis of laminitis; however, laminar cell types responding to insulin remain poorly characterised. Objective: To identify laminar cell types expressing insulin receptor (IRc) and/or insulin-like growth factor-1 receptor (IGF-1R); and to evaluate the effect of dietary nonstructural carbohydrate (NSC) on their expression. Methods: Mixed-breed ponies (n = 22) received a conditioning hay chop diet (NSC ∼6%); following acclimation, ponies were stratified into lean (n = 11, body condition score [BCS]≤4) or obese (n = 11, BCS ≥7) groups and ea...
