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.
Fujiyama M, Jones T, Duke-Novakovski T.To evaluate perioperative stress-related hormones in isoflurane-anesthetized horses administered infusions of dexmedetomidine alone or with butorphanol or remifentanil, compared with ketamine-morphine. Methods: Randomized, prospective, nonblinded clinical study. Methods: A total of 51 horses undergoing elective surgical procedures. Methods: Horses were premedicated with xylazine, anesthesia induced with ketamine-diazepam and maintained with isoflurane and one of four intravenous infusions. Partial intravenous anesthesia (PIVA) was achieved with dexmedetomidine (1.0 μg kg hour; group D; 12 hor...
Lindåse S, Nostell K, Bergsten P, Forslund A, Bröjer J.Proxies are mathematical calculations based on fasting glucose and/or insulin concentrations developed to allow prediction of insulin sensitivity (IS) and β-cell response. These proxies have not been evaluated in horses with insulin dysregulation. The first objective of this study was to evaluate how fasting insulin (FI) and proxies for IS (1/Insulin, reciprocal of the square root of insulin (RISQI) and the quantitative insulin sensitivity check index (QUICKI)) and β-cell response (the modified insulin-to-glucose ratio (MIRG) and the homeostatic model assessment of β-cell function (HOMA-β)...
Bradbery AN, Coverdale JA, Hartz CJ, Millican AA, Goehring MS, Fikes KK, Picking E, Hammer CJ, Dunlap KA, Cardoso RC, Wickersham TA, Leatherwood JL....Results from previous studies indicate that maternal overnutrition during late gestation predisposes foals to metabolic disease, however, specific mechanisms resulting in disease remain unknown. Quarter Horse mares (n = 16), were randomly assigned to dietary treatments, beginning on gestational day 235, and consisted of a control group (CON- diet meeting nutrient requirement; n = 8) or an overfed diet (HIGH; n = 8) where mares received an additional 40 % above CON. On gestational days 285 and 315, an intravenous glucose tolerance test (FSIGTT) was conducted. Following parturition, foals were s...
Ribeiro RM, Ribeiro DS, Cota LO, Leme FO, M Carvalho A, Faleiros RR.This study aimed to characterize and correlate physiological and metabolic changes in horses fed a hypercaloric diet (HD). Nine mature horses with a mean initial body condition score of 2.9 ± 1 (scale, 1-9) were fed a high-calorie diet for 5 months. Fasting blood samples were collected before the study and biweekly for the duration of the project to determine the concentrations of cholesterol (CHOL), very low (VLDL), low (LDL) and high-density (HDL) lipoproteins, triglycerides, non-esterified fatty acids, and fructosamine. A low-dose oral glucose tolerance test (LGTT) was conducted before, 75...
Bourebaba L, Kornicka-Garbowska K, Al Naem M, Röcken M, Łyczko J, Marycz K.Protein tyrosine phosphatase 1B (PTP1B) is one of the major negative regulators of leptin and insulin signaling, and has been strongly implicated in insulin resistance development in the course of obesity and metabolic syndrome conditions; however, its exact role in controlling adipose tissue biogenesis is still poorly understood. This investigation aimed to elucidate whether selective inhibition of PTP1B using MSI-1436 compound may improve and restore the defective adipogenicity of ASCs isolated from EMS-affected horses. Equine ASC EMS cells were cultured under adipogenic conditions in the pr...
Delarocque J, Frers F, Huber K, Jung K, Feige K, Warnken T.Insulin dysregulation (ID) is an equine endocrine disorder, which is often accompanied by obesity and various metabolic perturbations. The relationship between weight variations and fluctuations of the insulin response to oral glucose tests (OGT) as well as the metabolic impact of ID have been described previously. The present study seeks to characterize the concomitant metabolic impact of variations in the insulin response and bodyweight during repeated OGTs using a metabolomics approach. Methods: Nineteen Icelandic horses were subjected to five OGTs over one year and their bodyweight, insuli...
Delarocque J, Reiche DB, Meier AD, Warnken T, Feige K, Sillence MN.Insulin dysregulation (ID) is a key risk factor for equine endocrinopathic laminitis, but in many cases ID can only be assessed accurately using dynamic tests. The identification of other biomarkers could provide an alternative or adjunct diagnostic method, to allow early intervention before laminitis develops. The present study characterised the metabolome of ponies with varying degrees of ID using basal and postprandial plasma samples obtained during a previous study, which examined the predictive power of blood insulin levels for the development of laminitis, in ponies fed a high-sugar diet...
Box JR, Karikoski NP, Tanskanen HE, Raekallio MR.Alpha-2-adrenoceptor agonists are sedatives that can cause fluctuations in serum insulin and blood glucose (BG) concentrations in horses. The objectives of this study were to investigate the effects of detomidine and vatinoxan on BG, insulin, and glucagon concentrations in horses with and without insulin dysregulation (ID). In a blinded cross-over design, eight horses with ID and eight horses without ID were assigned to each of four treatments: detomidine (0.02 mg/kg; DET), vatinoxan (0.2 mg/kg; VAT), detomidine + vatinoxan (DET + VAT), and saline control (SAL). Blood samples were taken at 0, ...
Kinsella HM, Hostnik LD, Rings LM, Swink JM, Burns TA, Toribio RE.The endocrine pancreas and hypothalamic-pituitary-adrenal axis (HPAA) are central to energy homeostasis, but information on their dynamics in response to energy challenges in healthy newborn foals is lacking. Objective: To evaluate glucagon, insulin, ACTH, and cortisol response to fasting and carbohydrate administration in healthy foals. Methods: Twenty-two healthy Standardbred foals ≤4 days of age. Methods: Foals were assigned to fasted (n = 6), IV glucose (IVGT; n = 5), PO glucose (OGT; n = 5), and PO lactose (OLT; n = 6) test groups. Blood samples were collected frequently for 210 min...
Gehlen H, Schwarz B, Bartmann C, Gernhardt J, Stöckle SD.Appropriate medical care for donkeys is challenging despite being important working animals in non-industrialized countries and pets in first world countries. Although the same principles of diagnosis and therapy as in horses are commonly applied, there are differences in reference values and physiologic reaction to dynamic tests. However, donkeys seem to suffer from typical equine diseases, such as metabolic syndrome and pituitary pars intermedia dysfunction (PPID). Asinine metabolic syndrome (AMS) comprises obesity, insulin dysregulation, and laminitis. The principles of diagnosis are simila...
Delarocque J, Frers F, Feige K, Huber K, Jung K, Warnken T.Little is known about the implications of hyperinsulinemia on energy metabolism, and such knowledge might help understand the pathophysiology of insulin dysregulation. Objective: Describe differences in the metabolic response to an oral glucose test, depending on the magnitude of the insulin response. Methods: Twelve Icelandic horses in various metabolic states. Methods: Horses were subjected to 3 oral glucose tests (OGT; 0.5 g/kg body weight glucose). Basal, 120 and 180 minutes samples were analyzed using a combined liquid chromatography tandem mass spectrometry and flow injection analysis ...
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...
Thorringer NW, Weisberg MR, Jensen RB.The competition for customers increases the search for new grain processing methods for equine feed, but the effect on starch digestibility and metabolic responses varies. Therefore, to evaluate the effect of the processing methods, toasting and micronizing, on starch digestion and the effect on metabolic responses, the mobile bag technique (MBT) and plasma glucose and insulin concentrations in the blood were used to estimate nutrient disappearance and metabolic responses pre-cecally. Further, cecal pH, ammonium nitrogen (N), and short-chain fatty acid (SCFA) concentrations were used to estima...
Rahnama S, Vathsangam N, Spence R, Medina-Torres CE, Pollitt CC, de Laat MA, Bailey SR, Sillence MN.Currently, there are no registered veterinary drugs for the treatment of endocrinopathic equine laminitis, and although this form of the disease is known to be caused by prolonged hyperinsulinaemia, the mechanism of insulin toxicity is unclear. One possibility is that high concentrations of insulin activate IGF-1 receptors (IGF-1R) in lamellar tissue, leading to uncontrolled cell proliferation and epidermal lamellar dysregulation. An equinized version of a human anti-IGF-1R therapeutic monoclonal antibody (mAb11) was generated to test this theory, using a modification of the prolonged euglycae...
Loos CMM, McLeod KR, Stratton SC, van Doorn DA, Kalmar ID, Vanzant ES, Urschel KL.Activation of the mechanistic target of rapamycin (mTOR)-controlled anabolic signaling pathways in skeletal muscle of rodents and humans is responsive to the level of dietary protein supply, with maximal activation and rates of protein synthesis achieved with 0.2 to 0.4 g protein/kg body weight (BW). In horses, few data are available on the required level of dietary protein to maximize protein synthesis for maintenance and growth of skeletal muscle. To evaluate the effect of dietary protein level on muscle mTOR pathway activation, five mares received different amounts of a protein supplement t...
Rahnama S, Spence R, Vathsangam N, Baskerville CL, Bailey SR, de Laat MA, Anderson ST, Pollitt CC, Sillence MN.Although it is understood that equine endocrinopathic laminitis can be triggered by high concentrations of insulin, it is unclear whether this represents a direct action on lamellar tissue via insulin receptors (InsR), an interaction with IGF-1 receptors (IGF-1R), or some other, indirect action. This uncertainty is because of the reported scarcity of InsR in lamellar tissue and the low affinity of insulin for equine IGF-1R. In the present study, the effects of insulin and IGF-1 (as a positive control) were examined using lamellar explants isolated from the hooves of healthy horses and incubate...
Miller AB, Loynachan AT, Bush HM, Hart KA, Barker VD, Campana-Emard AG, Grubbs ST, Adams AA.It remains unclear how pituitary pars intermedia dysfunction (PPID) and pergolide treatment (Prascend [pergolide tablets]) affect endocrine and immune function in horses. To evaluate these effects, blood was collected regularly from 28 university-owned horses (10 Non-PPID, 9 PPID control [PC], and 9 PPID treatment [PT]) over approximately 15 mo. Pergolide treatment was initiated after Day 0 collections. Analyses included ACTH, insulin, total cortisol, free cortisol, complete blood counts, plasma myeloperoxidase, and cytokine/receptor gene expression in basal whole blood and in vitro stimulat...
Patterson Rosa L, Mallicote MF, Long MT, Brooks SA.An analogous condition to human metabolic syndrome, Equine Metabolic Syndrome (EMS) is defined by several clinical signs including obesity, hyperinsulinemia, and peripheral insulin dysregulation (ID). Affected horses may also exhibit hypertension, hyperlipemia and systemic inflammation. Measures of ID typically comprise the gold-standard for diagnosis in veterinary care. Yet, the dynamic nature of insulin homeostasis and complex procedures of typical assays make accurate quantification of ID and EMS challenging. This work aimed to investigate new strategies for identification of biochemical ma...
Nostell K, Lindåse S, Winqvist E, Bröjer J.Obesity is associated with insulin resistance, vascular dysfunction and altered cortisol metabolism both in humans and in horses. Objective: Evaluate the effect of weight gain induced by a haylage diet low in nonstructural carbohydrates (NSC) on insulin sensitivity, blood pressure and serum cortisol concentrations. Methods: In vivo experiment. Methods: Nine adult Standardbred mares fed a fat supplemented haylage diet at 250% of the horses' daily metabolisable energy requirements for 22 weeks. Horses were then turned out on pasture for 4 weeks. Insulin sensitivity (SI ) was measured before an...
Stokes SM, Burns TA, Watts MR, Bertin FR, Stefanovski D, Medina-Torres CE, Belknap JK, van Eps AW.Continuous digital hypothermia (CDH) prevents lamellar failure in the euglycemic hyperinsulinemic clamp (EHC) model of laminitis, but the protective mechanisms are unclear. Objective: To determine if CDH inhibits lamellar inflammatory signaling in the EHC model of laminitis. Methods: Eight Standardbred horses. Methods: Prospective experimental study. Horses underwent an EHC, with 1 forelimb treated with CDH and the other kept at ambient temperature (AMB). Horses were euthanized 48 hours after initiation of the EHC and lamellar tissue was analyzed via polymerase chain reaction (pro-inflammato...
Box JR, McGowan CM, Raekallio MR, Mykkänen AK, Carslake H, Karikoski NP.Obesity and insulin dysregulation (ID) predispose horses to laminitis. Determination of management practices or phenotypic markers associated with ID may benefit animal welfare. Objective: Determine ID status of a population of Finnhorses using an oral sugar test (OST) and compare phenotypes and management factors between ID and non-ID Finnhorses. Methods: One hundred twenty-eight purebred Finnhorses ≥3 years of age. Methods: Owners were recruited using an online questionnaire regarding signalment, history, feeding, and exercise of their horses. Selected contributing stables within a prede...
Rahnama S, Vathsangam N, Spence R, Anderson ST, de Laat MA, Bailey S, Sillence MN.Prolonged hyperinsulinemia is thought to be the cause of equine endocrinopathic laminitis, a common and crippling disease of the foot, for which there are no pharmacologic treatments other than pain relief. It has been suggested that insulin causes its effects on the lamellae by activating IGF-1 receptors (IGF-1R), as insulin receptors (InsR) are scarce in this tissue, whereas IGF-1R are abundant and become downregulated after prolonged insulin infusion. As a first step toward confirming this mechanism and beginning to develop a therapeutic anti-IGF-1R monoclonal antibody (mAb) for horses, it ...
Salinas C, Espinosa G, Morales N, Henríquez C, Morán G, Gajardo G, Uberti B.Obesity is a highly prevalent condition in horses. Dysfunctional neutrophil activity has been reported in metabolically healthy obese humans, but minimal data exist regarding horses. The present study evaluated the effect of obesity on apoptosis, phagocytosis and oxidative burst activity of peripheral blood neutrophils from lean and obese non-insulin dysregulated horses. Seven lean (BCS, body condition score 4-6/9) and five obese (BCS 8-9) horses were enrolled in the study. All animals underwent two metabolic tests (OGT, oral glucose test; IRT, insulin response test) before their selection to ...
Campolo A, Frantz MW, de Laat MA, Hartson SD, Furr MO, Lacombe VA.Endocrinopathic laminitis is pathologically similar to the multi-organ dysfunction and peripheral neuropathy found in human patients with metabolic syndrome. Similarly, endocrinopathic laminitis has been shown to partially result from vascular dysfunction. However, despite extensive research, the pathogenesis of this disease is not well elucidated and laminitis remains without an effective treatment. Here, we sought to identify novel proteins and pathways underlying the development of equine endocrinopathic laminitis. Healthy Standardbred horses ( = 4/group) were either given an electrolyte in...
Delarocque J, Frers F, Huber K, Feige K, Warnken T.Insulin dysregulation (ID) goes along with lasting or transient hyperinsulinemia able to trigger equine laminitis, a painful and crippling foot condition. Promoting weight loss through dietary changes and physical activity is currently the main option to prevent this disease. This study aimed at describing the relationship between weight variations and the level of ID as determined by oral glucose tests (OGT). Therefore, the insulin response of 19 Icelandic horses to repeated OGTs was retrospectively analysed considering the variations in their body weight. Results: There was a strong linear r...
Żak A, Siwińska N, Chełmecka E, Bażanów B, Romuk E, Adams A, Niedźwiedź A, Stygar D.The study aims to assess the impact of age, pituitary pars intermedia dysfunction (PPID) and insulin dysregulation (ID) in horses on selected oxidative stress markers. The study includes 32 horses, divided into three groups: "young" adult group (aged 8-16 years old) "geriatric" group (aged 18-24 years old) and the "PPID" group (aged 15-31 years old). The PPID group was further divided into two subgroups: PPID ID+ and PPID ID- based on presence or absence of ID. We measured serum antioxidant stress markers in all horses: total oxidant status (TOS), total antioxidant capacity (TAC), ceruloplasmi...
Roy MM, Norton EM, Rendahl AK, Schultz NE, McFarlane D, Geor RJ, Mickelson JR, McCue ME.An 11G nucleotide repeat in the 3' UTR of FAM174A was recently postulated as a risk allele with a dominant mode of inheritance for equine metabolic syndrome (EMS) and laminitis status in Arabian horses. The objective of this project was to evaluate this hypothesis in a large and diverse across-breed population. A total of 301 ponies, 292 Morgans, 64 Arabians, 49 Tennessee Walking Horses and 59 Quarter Horses were genotyped for six observed G repeat alleles in the FAM174A 3' UTR. Phenotype data included laminitis status, baseline insulin, glucose, non-esterified fatty acids, triglycerides, adip...
d' Fonseca NMM, Gibson CME, van Doorn DA, de Ruijter-Villani M, Stout TAE, Roelfsema E.Overfeeding is associated with obesity and insulin dysregulation (ID), which are both risk factors for equine metabolic syndrome. How chronic overfeeding affects development of these factors is poorly understood. Objective: To examine the influence of long-term high-energy diet provision on body condition and ID. Methods: Eleven Shetland pony mares. Methods: In a 3-phase study, the high-energy group (n = 7) was fed 200% of net energy (NE) requirements (hay; concentrate: 36% sugar and starch, 13% fat) for 24 weeks, followed by 17 weeks hay-only feeding before resuming the high-energy diet (...
Fitzgerald DM, Spence RJ, Stewart ZK, Prentis PJ, Sillence MN, de Laat MA.The equine microbiome can change in response to dietary alteration and may play a role in insulin dysregulation. The aim of this study was to determine the effect of adding pasture to a hay diet on the faecal bacterial microbiome of both healthy and insulin-dysregulated ponies. Faecal samples were collected from 16 ponies before and after dietary change to enable bacterial 16S rRNA sequencing of the V3-V4 region. The dominant phyla in all samples were the Firmicutes and Bacteroidetes. The evenness of the bacterial populations decreased after grazing pasture, and when a pony was moderately insu...
Spears JW, Lloyd KE, Siciliano P, Pratt-Phillips S, Goertzen EW, McLeod SJ, Moore J, Krafka K, Hyda J, Rounds W.Forty-eight Quarter Horse geldings (3 to 8 yr of age) were used to determine the effects of dietary chromium (Cr), in the form of Cr propionate (Cr Prop) on insulin sensitivity. Horses were blocked by age, body condition score, and glucose response to concentrate feeding on day 0 and randomly assigned to treatments. Treatments consisted of 0, 2, 4, or 8 mg Cr/d from Cr Prop. Horses were fed daily a concentrate mix at a rate of 0.2 kg/100 kg body weight (BW) and grass hay at 1.75 to 2.0 kg/100 kg BW. All horses were fed the control diet for 7 d prior to the initiation of the study. After an ove...
Asplin KE, Curlewis JD, McGowan CM, Pollitt CC, Sillence MN.Several conditions associated with laminitis in horses are also associated with insulin resistance, which represents the failure of glucose uptake via the insulin-responsive glucose transport proteins in certain tissues. Glucose starvation is a possible mechanism of laminitis, but glucose uptake mechanisms in the hoof are not well understood. Objective: To determine whether glucose uptake in equine lamellae is dependent on insulin, to characterise the glucose transport mechanism in lamellae from healthy horses and ponies, and to compare this with ponies with laminitis. Methods: Study 1 investi...
Ginther OJ, Bergfelt DR, Beg MA, Meira C, Kot K.In cattle and mares, free insulin-like growth factor 1 (IGF-1) is higher in the future dominant follicle (F1) than in the future largest subordinate follicle (F2) before deviation in diameter or selection is manifested between the two follicles. The effect of IGF-1 on other follicular-fluid factors and on the destiny of F2 were studied in two experiments in each species, using a total of 40 heifers and 42 mares. An injection of IGF-1 was made into F2 at the expected beginning of deviation (heifers, F1 >or= 8.5 mm; mares, F1 >or= 20.0 mm; Hour 0). In heifers, follicular fluid was taken fr...
Wray H, Elliott J, Bailey SR, Harris PA, Menzies-Gow NJ.The mechanisms underlying individual animal predisposition to pasture-associated laminitis remain unclear; however, chronic inflammation is implicated. Objective: To identify differences in the inflammatory profile of a group of previously laminitic ponies compared with control animals at pasture in late spring and winter. Methods: Previously laminitic (PL; n = 38 and 42) and nonlaminitic control ponies (NL; n = 41 and 39) were sampled in late spring and winter. Body condition score, height, weight and crest height and thickness were measured. Plasma concentrations of tumour necrosis factor-α...
The Journal of nutritionJune 15, 2006
Volume 136, Issue 7 Suppl 2094S-2098S doi: 10.1093/jn/136.7.2094S
Treiber KH, Kronfeld DS, Geor RJ.Insulin is a major regulatory hormone in glucose and fat metabolism, vascular function, inflammation, tissue remodeling, and the somatotropic axis of growth. Insulin resistance alters insulin signaling by decreasing insulin action in certain resistant pathways while increasing insulin signaling in other unaffected pathways via compensatory hyperinsulinemia. In humans, altered insulin signaling is implicated in reduced glucose availability to insulin-sensitive cells, vasoconstriction and endothelial damage, and inflammatory response. Although no direct evidence exists for insulin's role in thes...
Selim S, Elo K, Jaakkola S, Karikoski N, Boston R, Reilas T, Särkijärvi S, Saastamoinen M, Kokkonen T.Obesity and insulin resistance have been shown to be risk factors for laminitis in horses. The objective of the study was to determine the effect of changes in body condition during the grazing season on insulin resistance and the expression of genes associated with obesity and insulin resistance in subcutaneous adipose tissue (SAT). Sixteen Finnhorse mares were grazing either on cultivated high-yielding pasture (CG) or semi-natural grassland (NG) from the end of May to the beginning of September. Body measurements, intravenous glucose tolerance test (IVGTT), and neck and tailhead SAT gene exp...
Borgia L, Valberg S, McCue M, Watts K, Pagan J.The aim of this study was to determine whether the glycaemic/insulinaemic responses to hay with non-structural carbohydrate (NSC, soluble carbohydrate) of 17% (HC), 10% (MC) or 4% (LC) differs in control horses and whether these responses differ between control and horses with polysaccharide storage myopathy (PSSM). Five clinically normal control horses and seven PSSM horses, all unfit and of Quarter Horse breeding (age 9.4 ± 3.4 years, body condition score range: 4.5-6). A crossover design compared the HC and LC hay, with horses randomly assigned to hay type for 5 days, and all horses fed th...
Lacombe VA, Hinchcliff KW, Devor ST.To characterize insulin-sensitive glucose-transporter (GLUT-4) protein in equine tissues and determine effects of exercise and glucose administration on content of GLUT-4 protein in equine skeletal muscle. Methods: Tissue samples from 9 horses. Methods: Western blot analyses were performed on crude membrane preparations of equine tissues to characterize GLUT-4. In a crossover, randomized study, horses were strenuously exercised for 3 consecutive days and then administered 13.5% glucose or isotonic saline (0.9% NaCl; control) solution, i.v., at similar infusion rates for 12.1 hours. Samples wer...
Delarocque J, Frers F, Feige K, Huber K, Jung K, Warnken T.Little is known about the implications of hyperinsulinemia on energy metabolism, and such knowledge might help understand the pathophysiology of insulin dysregulation. Objective: Describe differences in the metabolic response to an oral glucose test, depending on the magnitude of the insulin response. Methods: Twelve Icelandic horses in various metabolic states. Methods: Horses were subjected to 3 oral glucose tests (OGT; 0.5 g/kg body weight glucose). Basal, 120 and 180 minutes samples were analyzed using a combined liquid chromatography tandem mass spectrometry and flow injection analysis ...
Mendoza FJ, Estepa JC, Gonzalez-De Cara CA, Aguilera-Aguilera R, Toribio RE, Perez-Ecija A.Donkeys are commonly afflicted by endocrine and metabolic disturbances but few studies have investigated endocrine variables involved in energy regulation and their association with morphometric indices, age or gender in this species. Hemostatic and clinical differences have been demonstrated between horses and donkeys, so to consider both species as metabolically and endocrinologically similar could lead to misdiagnosis. In this study, plasma concentrations of glucose, triglycerides and endocrine factors involved in energy homeostasis (insulin, glucagon, leptin, adiponectin, ghrelin and insul...
Freestone JF, Beadle R, Shoemaker K, Bessin RT, Wolfsheimer KJ, Church C.Ten hyperinsulinaemic ponies divided into conditioned (N = 5) and rested (N = 5) groups were evaluated for their insulin and glucose response following oral glucose administration at Weeks 0, 2, 4, and 6. All ponies received a controlled intake of a pelleted ration during the study. In both groups body weight had decreased from baseline by Week 4 and remained low. After 2 weeks of exercise, ponies in the conditioned group had significantly decreased insulin and glucose indices, including peak insulin response, area under the insulin curve from 0 to 210 min (TIS), and the TIS value: area under ...
Kirkwood NC, Hughes KJ, Stewart AJ.Substantial morbidity results from pituitary pars intermedia dysfunction (PPID) which is often underestimated by owners and veterinarians. Clinical signs, pathophysiology, diagnostic tests, and treatment protocols of this condition are reviewed. The importance of improved recognition of early clinical signs and diagnosis are highlighted, as initiation of treatment will result in improved quality of life. Future research should be targeted at improving the accuracy of the diagnosis of PPID, as basal adrenocorticotropic hormone (ACTH) concentration can lack sensitivity and thyrotropin releasing ...
Toribio RE, Kohn CW, Rourke KM, Levine AL, Rosol TJ.To determine effects of experimentally induced hypercalcemia on serum concentrations and urinary excretion of electrolytes, especially ionized magnesium (iMg), in healthy horses. Methods: 21 clinically normal mares. Methods: Horses were assigned to 5 experimental protocols (1, hypercalcemia induced with calcium gluconate; 2, hypercalcemia induced with calcium chloride; 3, infusion with dextrose solution; 4, infusion with sodium gluconate; and 5, infusion with saline [0.9% NaCl] solution). Hypercalcemia was induced for 2 hours. Dextrose, sodium gluconate, and saline solution were infused for 2 ...
Menzies-Gow NJ, Wray H, Bailey SR, Harris PA, Elliott J.The mechanisms underlying predisposition to pasture-associated laminitis remain unclear; chronic inflammation is implicated, and this may be exacerbated by physical inactivity. Objective: To determine whether exercise affects the inflammatory profile of normal and previously laminitic ponies. Methods: Prospective case-control study. Methods: The short (1 day) and longer term (14 days) effects of low intensity (10 min walking and 5 min trotting) exercise on plasma inflammatory marker concentrations in normal (NL) and previously laminitic (PL) nonobese ponies (n = 6/group) was determined. Plasma...
Ropka-Molik K, Stefaniuk-Szmukier M, Z Ukowski K, Piórkowska K, Bugno-Poniewierska M.It has been found that Arabian and Thoroughbred horses differ in muscle fiber structure and thus in physiological changes occurring in muscles during exercise. The aim of the present study was to identify the global gene expression modifications that occur in skeletal muscle following a training regime to prepare for flat racing. Whole transcriptomes of muscle (gluteus medius) were compared between three time points of tissue collection: T (untrained horses), T (horses after intense gallop phase), and T (horses at the end of racing season), 23 samples in total. The numerous groups of exercise-...
Durham AE, Hughes KJ, Cottle HJ, Rendle DI, Boston RC.Type 2 diabetes mellitus (T2DM) is diagnosed rarely in equine practice although it may be under-recognised. A greater awareness of the condition and therapeutic considerations would be to the benefit of such cases presenting in practice. More investigation into the pharmacological management of these cases is needed. Objective: Three cases of diabetes mellitus were investigated using a specific test for insulin sensitivity and pancreatic beta cell function in order to define accurately and characterise the existence of T2DM in all 3 subjects. Methods: The insulin-modified frequently sampled i....
Fitzgerald DM, Walsh DM, Sillence MN, Pollitt CC, de Laat MA.Supraphysiological insulin and incretin responses to a cereal-based diet have been described in horses and ponies with insulin dysregulation (ID). However, the hormonal responses to grazing have not yet been described. Objective: To determine if there is a difference in the insulin and incretin responses to grazing pasture between insulin-dysregulated and healthy ponies. Methods: A cohort of 16 ponies comprising 5 with normal insulin regulation (NIR), 6 with moderate ID (MID), and 5 with severe ID (SID). Methods: In this case-control study, an oral glucose test (OGT) was used to determine the ...
Waller AP, Huettner L, Kohler K, Lacombe VA.Although insulin resistance (IR) has been increasingly recognized in horses, a clear understanding of its pathophysiology is lacking. The purpose of the present study was to determine the early pathologic changes in IR horses by characterizing alterations in proteins that play key roles in innate immunological responses and inflammatory pathways, and by identifying potential links with glucose transport and insulin signaling. Visceral (VIS) and subcutaneous (SC) adipose tissue and skeletal muscle (SM) biopsies were collected from horses, which were classified as insulin-sensitive (IS) or IR ba...
Sykes BW, Furr MO.The pathophysiology of endotoxaemia, a leading cause of death in the horse, is beginning to be understood in greater detail. Endotoxin may be absorbed into the systemic circulation in a number of different ways: most commonly the body's normal defense mechanisms are disrupted or bypassed, or the normal clearance mechanisms overwhelmed. Following this wide-spread effects are observed, although the most significant are seen in the cardiovascular system. Fever, arterial hypoxaemia and signs of abdominal pain are also common. With increased understanding of the disease new therapeutic agents have ...
Tóth F, Frank N, Elliott SB, Perdue K, Geor RJ, Boston RC.The frequently sampled i.v. glucose tolerance test (FSIGTT) is used to evaluate glucose and insulin dynamics in horses, but it has not been determined whether urinary glucose spilling (UGS) affects results. Objective: UGS occurs in horses during the FSIGTT and this problem can be minimised by adjusting the dextrose and insulin dosages used. Methods: Six mature mares were included in this study. In the first phase, 6 FSIGTT procedures were performed in each horse to evaluate 6 different dextrose dosages. Six different insulin dosages were evaluated during the second phase of the study after adm...
Loos CMM, Dorsch SC, Elzinga SE, Brewster-Barnes T, Vanzant ES, Adams AA, Urschel KL.Equine metabolic syndrome (EMS) is characterized by an abnormal insulin response to a glycemic challenge but despite the known insulinotropic effects of certain amino acids, there is a paucity of data evaluating the impact of dietary protein on insulin dynamics in these horses. The objective was therefore to assess insulin and amino acid responses following intake of a high protein meal in healthy horses and those with EMS. Six mature horses diagnosed with EMS and six age-matched control horses without EMS were used. Horses were fed 2g/kg body mass (BM) of a high protein pellet (31% crude prot...
Tóth F, Frank N, Chameroy KA, Bostont RC.Insulin resistance (IR) is a risk factor for pasture-associated laminitis in equids and alimentary carbohydrate overload may trigger laminitis. Whether glucose metabolism responses to carbohydrate overload are more pronounced in insulin-resistant horses requires further study. Objective: Horses pretreated with endotoxin to alter insulin sensitivity differ significantly in their glucose and insulin responses to carbohydrate overload. Methods: Horses (n=24) were divided into 3 groups. A lipopolysaccharide (LPS; n=8) group that received endotoxin as an 8 h 7.5 ng/kg bwt/h i.v. continuous rate inf...
Cartmill JA, Thompson DL, Storer WA, Gentry LR, Huff NK.Previous observations from this laboratory indicated that horses with high BCS could have resting plasma leptin concentrations ranging from low (1 to 5 ng/mL) to very high (10 to 50 ng/mL). To study the possible interactions of leptin secretion with other endocrine systems, BCS and plasma leptin concentrations were measured on 36 mares and 18 geldings. From mares and geldings that had a mean BCS of at least 7.5, five with the lowest (low leptin) and five with the highest (high leptin) leptin concentrations were selected. Jugular blood samples were collected twice daily for 3 d from the 20 sele...
Murphy DJ, Nixon AJ.To examine the site-specific and dose-dependent effects of insulin-like growth factor I (IGF-I) on normal equine tendon in vitro. Methods: Superficial digital flexor tendon explants derived from a euthanatized 3-year-old horse. Methods: Explants in culture were treated with 0, 100, 250, or 500 ng of IGF-I/ml for 14 days with an end-stage radiolabel of 20 microCi of [3H]proline/ml or 5 microCi of [3H]thymidine/ml. The tendon tissues were then analyzed biochemically for hydroxyproline content by reverse-phase high-performance liquid chromatography, DNA content by fluorometry, and glycosaminoglyc...
Carslake HB, Argo CM, Pinchbeck GL, Dugdale AHA, McGowan CM.Reduction of the hyperinsulinaemic response to feeding is central to the management of insulin dysregulation (ID). The aim of this study was to compare insulinaemic and glycaemic responses to soaked hay, dry hay and haylage in ponies. Twelve ponies of mixed breeds were maintained under identical management conditions. A randomised four-way crossover trial was conducted, in which fasted animals were fed a meal of 0.25% body weight as dry matter intake soaked hay, dry hay or haylage, or administered an oral glucose test (OGT). Blood glucose and serum insulin concentrations were measured before a...
Funk RA, Wooldridge AA, Stewart AJ, Behrend EN, Kemppainen RJ, Zhong Q, Johnson AK.Equine metabolic syndrome (EMS) is an increasingly recognized problem in adult horses. Affected horses are often obese and predisposed to the development of laminitis, especially in the spring and summer months. In addition, in the summer and fall months, increases in endogenous insulin concentrations, a marker of EMS, have been reported. Objective: The purpose of this study was to evaluate seasonal changes in results of the combined glucose-insulin tolerance test (CGIT), a diagnostic test for EMS. Methods: Nine healthy, aged horses with no history of laminitis and no clinical signs of EMS. Me...
Silver M, Fowden AL, Knox J, Ousey JC, Franco R, Rossdale PD.The effects of insulin-induced hypoglycaemia on plasma catecholamines, cortisol and metabolites have been examined in newborn and 7-14-day-old foals. The fall in plasma glucose elicited by the highest dose of insulin (1.0 i.u./kg) given to the neonates was slower in onset and less severe in effect than 0.5 i.u./kg in the older foals. There was a significant inverse correlation between the concentrations of glucose and adrenaline (but not noradrenaline) in plasma once the glucose level had fallen below 2 mmol/l; the adrenergic response to hypoglycaemia was greater in the 7-14-day-old foals than...
Barsnick RJ, Hurcombe SD, Smith PA, Slovis NM, Sprayberry KA, Saville WJ, Toribio RE.Endocrine dysregulation of hormones of energy metabolism is well documented in critically ill humans, but limited information exists in septic foals. The purpose of this study was to provide information on the hormonal response to energy metabolism in critically ill foals, focusing on insulin, glucagon, and leptin. Objective: Concentrations of insulin, glucagon, leptin, and triglycerides will be higher, whereas glucose concentration will be lower in septic foals than in healthy and sick nonseptic foals. The magnitude of these differences will be associated with severity of disease and nonsurvi...
Connysson M, Essén-Gustavsson B, Lindberg JE, Jansson A.A higher forage allowance to athletic horses might be an alternative to increase health and the gut fluid reservoir. However, more forage might increase bodyweight (bwt) and could therefore be a limitation during competition. Objective: To investigate the effect of a forage-only diet (FD) compared to a 50:50 (dry matter basis) forage:oats diet (OD) on bwt, plasma protein concentration and some metabolic plasma parameters during 12 h of feed deprivation. Methods: Twelve adult Standardbred horses in training were used. The 2 diets were fed in 2 experimental periods of 3 weeks each in a crossover...
Kubota M, Nagasaki M, Tokudome M, Shinomiya Y, Ozawa T, Sato Y.The present study was undertaken to analyze the acute and chronic effects of exercise on insulin sensitivity in elder diabetic patients using a horseback riding therapeutic equipment (Joba). The acute effects of exercise were examined by means of a single session of Joba riding that lasted for 30 min. The average glucose infusion rates (GIR) before and during exercise were regarded as an index of the insulin action in peripheral tissues by the euglycemic clamp. The chronic effects of exercise were studied by training the elder diabetic patients for 12 weeks using the Joba apparatus. The insuli...
Stewart-Hunt L, Geor RJ, McCutcheon LJ.Increased insulin sensitivity occurs after a period of exercise training, but the mechanisms underlying this training-associated increase in insulin action have not been investigated. Objective: To examine the effects of short-term endurance training (7 consecutive days) and a subsequent period of inactivity (5 days) on whole body insulin sensitivity and GLUT-4 protein and the activities of glycogen synthase (GS) and hexokinase (HK) in skeletal muscle. It was hypothesised that training would increase insulin sensitivity in association with increased GLUT-4 protein and activities of GS and HK, ...
