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.
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 ...
Hallman I, Karikoski N, Kareskoski M.Obesity is a growing welfare concern in modern equine populations and predisposes horses to disturbances in energy metabolism such as insulin dysregulation. However, equine metabolic syndrome has only been recognized in recent decades. Functioning energy metabolism is pivotal to normal body homeostasis and affects essentially all organ systems, including reproduction. Previous literature suggests that obesity has an effect not only on the reproductive processes in mares but also on offspring health, predisposing the offspring to later-onset orthopedic and metabolic problems. This review focuse...
Go YY, Hazard NW, Balasuriya UBR, Chapman AM, Fitton NS, Kenéz Á, Andrews FM.Accurate quantitative analysis of equine insulin in blood samples is critical for assessing hyperinsulinemia in horses. Although there are various laboratory methods for evaluating equine serum insulin, different immunoassays show significant discrepancies between the determined insulin concentrations and are often not comparable. The aim of this study was to evaluate the Immulite® 1000 chemiluminescent immunoassay (CLIA) to establish independent laboratory and assay-specific cut values to provide an accurate diagnosis of hyperinsulinemia in horses. Thus, the analytical and clinical performan...
Kellon EM, Gustafson KM.Sodium-Glucose CoTransporter-2 (SGLT2) inhibitors, the -flozin group of drugs, which block glucose reuptake in the renal proximal tubule, are being increasingly used off-label to treat horses with refractory hyperinsulinemia. After 2 years of use by animals in our group, a horse on canagliflozin was incidentally noted to be hyperlipemic. We have been following a cohort of equines (n = 20) treated with SGLT2 inhibitors due to refractory hyperinsulinemia. The animals are owned by members of the Equine Cushing's and Insulin Resistance Group and treated by their attending veterinarians. The index ...
Bourebaba L, Serwotka-Suszczak A, Pielok A, Sikora M, Mularczyk M, Marycz K.Equine metabolic syndrome (EMS) is a multifactorial pathology gathering insulin resistance, low-grade inflammation and past or chronic laminitis. Among the several molecular mechanisms underlying EMS pathogenesis, increased negative insulin signalling regulation mediated by protein tyrosine phosphatase 1 B (PTP1B) has emerged as a critical axis in the development of liver insulin resistance and general metabolic distress associated to increased ER stress, inflammation and disrupted autophagy. Thus, the use of PTP1B selective inhibitors such as MSI-1436 might be considered as a golden therapeut...
Elliott J, Bailey SR.Equine laminitis has both fascinated and frustrated veterinary researchers and clinicians for many years. The recognition that many ponies suffering from pasture-associated laminitis have an insulin-dysregulated phenotype (endocrinopathic laminitis, EL) and that prolonged insulin and glucose infusions can experimentally induce laminar pathology and functional failure are seminal discoveries in this field. Researchers have studied the molecular basis for disease pathogenesis in models of EL, sepsis-related laminitis and supporting limb laminitis and generated much data over the last 15 years....
de Laat MA, Fitzgerald DM.Equine insulin dysregulation (ID) comprises amplified insulin responses to oral carbohydrates or insulin resistance, or both, which leads to sustained or periodic hyperinsulinaemia. Hyperinsulinaemia is important in horses because of its clear association with laminitis risk, and the gravity of this common sequela justifies the need for a better understanding of insulin and glucose homoeostasis in this species. Post-prandial hyperinsulinaemia is the more commonly identified component of ID and is diagnosed using tests that include an assessment of the gastrointestinal tract (GIT). There are se...
de Tonnerre DJ, Medina Torres CE, Stefanovski D, Robinson MA, Kemp KL, Bertin FR, van Eps AW.Sirolimus, a mechanistic target of rapamycin inhibitor, suppresses insulin production in other species and has therapeutic potential for hyperinsulinemia in horses. Objective: Determine the pharmacokinetics (PKs) of sirolimus and evaluate its effect on insulin dynamics in healthy and insulin dysregulation (ID) horses. Methods: Eight Standardbred geldings. Methods: A PK study was performed followed by a placebo-controlled, randomized, crossover study. Blood sirolimus concentrations were measured by liquid chromatography-mass-spectrometry. PK indices were estimated by fitting a 2-compartment mod...
Zapf AM, Fey K, Büttner K, Gröf M, Staszyk C.Pituitary pars intermedia dysfunction (PPID) and dental disorders are of major concern in horses older than 15 years. Although PPID in geriatric horses and dental disorders in all age groups are well described, a connection between this endocrine disease and pathological changes in equine dental structures has not yet been investigated. In humans, periodontitis is considered to be a complication of systemic diseases like diabetes mellitus type 2, obesity and various conditions leading to an impaired immune response. In PPID, cross links to insulin and immune dysregulations are proven. The aim ...
Li FI, Spence RJ, de Laat MA, Harris PA, Sonntag J, Menzies-Gow NJ, Durham AE, Bailey SR, Sillence MN.High concentrations of adrenocorticotropic hormone (ACTH) are used as an indicator of pituitary pars intermedia dysfunction (PPID), but other factors that may influence ACTH need to be understood, if diagnostic reference ranges for ACTH are to be used with confidence. Insulin dysregulation (ID) could be one such factor, as insulin affects pituitary hormones in other species. Objective: To test the hypothesis that a relationship exists between high insulin and high ACTH in aged (>15-year-old) animals with no clinical signs of PPID. Methods: A cohort study. Methods: Thirteen horses and eleven p...
Warnken T, Schaub C, Delarocque J, Frers F, Feige K, Sonntag J, Reiche DB.Oral glycemic challenge (GC) tests are recommended for diagnosis of insulin dysregulation (ID). Various protocols are used, but all have limitations in terms of palatability, ease of use, variable composition, geographic availability, or some combination of these. Objective: To evaluate newly developed formulations with defined carbohydrate composition for use as oral GCs. Methods: Thirty-four horses and ponies in various metabolic states. Methods: Our objectives were carried out in 2 separate cross-over experiments. First, the palatability and acceptance of various GCs (2 syrups, 1 granulate)...
de Laat MA, Warnken T, Delarocque J, Reiche DB, Grob AJ, Feige K, Carslake HB, Durham AE, Sillence MN, Thane KE, Frank N, Brojer J, Lindase S....A glycemic challenge test is used for the diagnosis of insulin dysregulation (ID) in horses and ponies. Different forms of the test exist where the administrative route and dose of glucose vary, which makes interpretation of results challenging. Objective: To evaluate the palatability of, and blood glucose and insulin responses to, carbohydrate pellets fed as an oral glucose test (OGT), and to establish the diagnostic threshold for ID when using the pellets. Methods: University and privately-owned horses and ponies (n = 157) comprised of 31 breeds and both sexes. Methods: Multicenter cohort ...
Manfredi JM, Jacob SI, Boger BL, Norton EM.Endocrinopathies affect multiple species in ever-increasing percentages of their populations, creating an opportunity to apply one-health approaches to determining creative preventative measures and therapies in athletes. Obesity and alterations in insulin and glucose dynamics are medical concerns that play a role in whole-body health and homeostasis in both horses and humans. The role and impact of endocrine disorders on the musculoskeletal, cardiovascular, and reproductive systems are of particular interest to the athlete. Elucidation of both physiologic and pathophysiologic mechanisms invol...
Macon EL, Harris P, Bailey S, Caldwell Barker A, Adams A.Identifying intake levels of nonstructural carbohydrates (NSCs) that limit the postprandial insulinaemic response in the insulin dysregulated (ID) horse may help reduce hyperinsulinaemia-associated laminitis (HAL) risk. Objective: To determine if ID horses have thresholds for pure sources of starch and sugar, above which there is an augmented insulin response. Methods: Randomised crossover experiment. Methods: Fourteen adult horses (6 ID and 8 noninsulin dysregulated, NID; matched for bodyweight) were randomly fed eight dietary treatments. Dietary treatments were formulated using a base of low...
Stoeckle SD, Timmermann D, Merle R, Gehlen H.Laminitic horses commonly suffer from an endocrine disease such as equine metabolic syndrome. Hyperinsulinemia is considered a key factor in the pathogenesis of laminitis. Since insulin also affects protein turnover in the body, the resting plasma amino acid concentrations of obese horses that were presented for a combined glucose insulin test (CGIT) were determined. In total, 25 obese horses and two lean horses with recurrent laminitis underwent a CGIT. Of these, five were not insulin dysregulated (obese), 14 were insulin dysregulated (ID), and eight were insulin-dysregulated and laminitic (I...
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...
