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.
Klinkhamer K, Menheere PP, van der Kolk JH.Glucocorticoids are suggested to precipitate laminitis and induce insulin resistance in horses. Objective: To assess insulin sensitivity and the basal amount of glucose metabolized in equine pituitary pars intermedia dysfunction (PPID). Methods: The euglycaemic hyperinsulinaemic clamp (EHC) technique was performed in seven horses with a diagnosis of PPID based on the presence of hypertrichosis and positive dexamethasone suppression-test results comprising one gelding and six mares with a mean age of 21.1 ± 5.8 (SD; range 15-34) years. Results were compared with those from five negative (h...
Wearn JG, Suagee JK, Crisman MV, Corl BA, Hulver MW, Hodgson DR, Geor RJ, McCutcheon LJ.Equine metabolic syndrome (EMS) is a condition of obese horses characterized by insulin resistance, systemic inflammation, and an increased risk of laminitis. The pathogenesis of EMS is thought, in part, to be due to inflammatory proteins produced by adipose tissue. Reducing inflammation may decrease the incidence of laminitis in horses with EMS. Pioglitazone hydrochloride, a thiazolidinedione, has efficacy to reduce obesity associated inflammation in humans. Eight normal, adult, horses were administered 1mg/kg pioglitazone for 14 days, and eight horses served as controls. Physical examination...
de Laat MA, Pollitt CC, Walsh DM, McGowan CM, Sillence MN.Persistent digital hyperthermia, presumably due to vasodilation, occurs during the developmental and acute stages of insulin-induced laminitis. The objectives of this study were to determine if persistent digital hyperthermia is the principal pathogenic mechanism responsible for the development of laminitis. The potent vasodilator, ATP-MgCl(2) was infused continuously into the distal phalanx of the left forefoot of six Standardbred racehorses for 48 h via intra-osseous infusion to promote persistent digital hyperthermia. The right forefoot was infused with saline solution and acted as an inter...
Witte TH, Yeager AE, Nixon AJ.OBJECTIVE-To evaluate outcome after intralesional injection of insulin-like growth factor-I (IGF-I) for treatment of superficial digital flexor (SDF) tendonitis in Thoroughbred racehorses. DESIGN-Retrospective case series. ANIMALS-40 Thoroughbred racehorses. PROCEDURES-Medical records of racehorses with SDF tendonitis treated within 13 weeks after injury by intralesional injection of IGF-I (25 or 50 μg every other day for 4 or 5 treatments) were reviewed. Outcome was determined via analysis of race records, owner follow-up, and examination. RESULTS-Mean age of the horses was 3.1 years (range,...
Salazar-Ortiz J, Camous S, Briant C, Lardic L, Chesneau D, Guillaume D.Mares have an annual reproductive rhythm, with a phase of inactivity in midwinter. The aim of this study was to determine the impact of food restriction on physiological and metabolic hallmarks of this rhythm. Methods: Over three successive years, 3 groups of 10 mares were kept under natural photoperiod. A 'well-fed' group was fed to maintain the mares in good body condition; a 'restricted' group received a diet calculated to keep the mares thin and a 'variable' group was fed during some periods like the 'restricted' group and during some other periods like the 'well-fed' group, with the aim o...
Eivers SS, McGivney BA, Gu J, MacHugh DE, Katz LM, Hill EW.Peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α) has emerged as a critical control factor in skeletal muscle adaptation to exercise, acting via transcriptional control of genes responsible for angiogenesis, fatty acid oxidation, oxidative phosphorylation, mitochondrial biogenesis and muscle fibre type composition. In a previous study, we demonstrated a significant increase in mRNA expression for the gene encoding PGC-1α (PPARGC1A) in Thoroughbred horse skeletal muscle following a single bout of endurance exercise. In this study, we investigated mRNA expression changes i...
de Laat MA, Sillence MN, McGowan CM, Pollitt CC.Endocrinopathic laminitis is frequently associated with hyperinsulinaemia but the role of glucose in the pathogenesis of the disease has not been fully investigated. This study aimed to determine the endogenous insulin response to a quantity of glucose equivalent to that administered during a laminitis-inducing, euglycaemic, hyperinsulinaemic clamp, over 48 h in insulin-sensitive Standardbred racehorses. In addition, the study investigated whether glucose infusion, in the absence of exogenous insulin administration, would result in the development of clinical and histopathological evidence of ...
Pereira GR, Lorenzo PL, Carneiro GF, Ball BA, Gonçalves PB, Pegoraro LM, Bilodeau-Goeseels S, Kastelic JP, Casey PJ, Liu IK.The objective of this study was to test the hypothesis that equine growth hormone (eGH), in combination with insulin growth factor-I (IGF-I), influences positively in vitro nuclear and cytoplasmic maturation of equine oocytes. Cumulus-oocyte complexes were recovered from follicles that were < 25 mm in diameter, characterized by morphology and were allocated randomly as follow: (a) control (no additives); (b) 400 ng/ml eGH; (c) 200 ng/ml IGF-I; (d) eGH + IGF-I; and (e) eGH + IGF-I + 400 ng/ml anti-IGF-I antibody. Oocytes were matured for 30 h at 38.5°C in air with 5% CO2 and then stained wi...
Knowles EJ, Withers JM, Mair TS.The use of plasma fructosamine concentration ([fructosamine]) as a marker of abnormal glucose homeostasis in laminitic horses has not been investigated. Objective: Plasma fructosamine concentration may be higher amongst laminitic horses than normal horses; this might relate to underlying insulin resistance. Objective: 1) To compare [fructosamine] between laminitic and normal horses. 2) To investigate associations between [fructosamine] at presentation in laminitic horses with a) single sample markers of insulin resistance and b) outcome. Methods: Plasma fructosamine concentration, fasting seru...
Karikoski NP, Horn I, McGowan TW, McGowan CM.Endocrinopathic causes of laminitis may be a common underlying causative pathogenesis in first-opinion or field cases presenting with laminitis, as opposed to laminitis produced in inflammatory research models. This study aimed to determine whether evidence of an underlying endocrinopathy was present in horses presented for laminitis to a first-opinion/referral veterinary teaching hospital. A second aim was to compare the signalment of horses and ponies with laminitis with the equine hospital population during the same period. All horses presenting for laminitis at Helsinki University Equine T...
Tinworth KD, Wynn PC, Boston RC, Harris PA, Sillence MN, Thevis M, Thomas A, Noble GK.Determining circulating equine insulin concentrations is becoming increasingly important in equine clinical practice and research. Most available assays are optimized for human medicine, but there is strong equine cross-reactivity because of the highly conserved nature of insulin. To identify an accurate and reliable assay for equine insulin, 6 commercial immunoassays were evaluated for precision, accuracy, and specificity. Only 1 assay initially reached the requisite standard: Mercodia Equine Insulin Enzyme-linked Immunosorbent assay (ELISA). Plasma matrix interferences were identified when t...
Stewart-Hunt L, Pratt-Phillips S, McCutcheon LJ, Geor RJ.Starch rich (S) feeds reduce insulin sensitivity in untrained horses when compared to high fat (F) feeds, but insulin sensitivity is not affected when S or F are fed during exercise training. The effects of S vs. F on training-associated alterations in skeletal muscle glucose metabolism are unknown. Objective: To determine the effects of dietary energy source on training-associated changes in insulin sensitivity, skeletal muscle GLUT4 protein and hexokinase (HK) and glycogen synthase (GS) activities in horses. Methods: After a baseline period on an all forage diet (Phase 1), horses were adapte...
Geor RJ, Stewart-Hunt L, McCutcheon LJ.There is limited information about factors regulating glucose utilisation post exercise in horses. Objective: To determine the effects of a single bout of moderate intensity exercise on measures of insulin-mediated (IMGU) and noninsulin-mediated (NIMGU) glucose uptake during a hyperglycaemic clamp (HC). Methods: Hyperglycaemic clamps were administered in random order to 8 Standardbreds under 4 conditions: 1) rest, insulinopenia (R-L); 2) rest, hyperinsulinaemia (R-H); 3) post exercise (45 min at ∼ 50% VO2peak), insulinopenia (Ex-L) and 4) post exercise, hyperinsulinaemia (Ex-H). In the R-L a...
Urschel KL, Geor RJ, Waterfall HL, Shoveller AK, McCutcheon LJ.Providing protein or amino acid mixtures in combination with glucose to post exercise in man has resulted in increases in the post feeding insulin response and in muscle glycogen and protein synthesis rates. However, whether protein and/or amino acids can modify the post exercise insulin responses in horses remains to be fully elucidated. Objective: To determine whether whey protein or leucine addition to a glucose solution affects the post gavage plasma insulin, glucose and amino acid responses in horses and whether these responses are different following a period of exercise vs. rest. Method...
Finno CJ, McKenzie E, Valberg SJ, Pagan J.Recurrent exertional rhabdomyolysis (RER) occurs in fit, nervous Thoroughbreds fed high nonstructural carbohydrate (NSC) diets. Clinical signs are diminished by feeding low NSC, high fat diets; however, the mechanism is unclear. Objective: To determine if the glucose, insulin and cortisol response to isocaloric diets varying in fat and NSC availability differ in fit vs. unfit Thoroughbreds with RER. Methods: Four fit (10 weeks treadmill training) RER Thoroughbred mares were exercised and fed 3 isocaloric (121 MJ/day) diets in a 5 day/diet block design. Two high NSC concentrates, sweet feed (SF...
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...
Shepherd ML, Pleasant RS, Crisman MV, Werre SR, Milton SC, Swecker WS.The objective of this study was to determine the effects of high and moderate non-structural carbohydrates (NSC) hay on insulin, glucose, triglyceride, and leptin concentrations in overweight Arabian geldings. Eight adult overweight (average BCS 7 [9-point scale]) Arabian geldings were fed each of two orchardgrass hays, high NSC (18% DM) and moderate NSC (12% DM), in a cross over design during two 28-day periods. Body weight and body condition score assessment along with blood sampling to measure insulin, glucose, leptin, and triglyceride concentrations were performed on days 0, 7, 14, 21 and ...
Suagee JK, Corl BA, Crisman MV, Hulver MW, McCutcheon LJ, Geor RJ.Laminitis is a painful, inflammatory disease of the equine hoof that often results in euthanasia. Elevated plasma insulin concentrations are a predictive factor for laminitis, and in previously healthy horses and ponies, laminitis was induced by infusion of insulin. Thus, we chose to determine if an infusion of insulin would increase plasma concentrations of inflammatory cytokines and cytokine mRNA abundance in subcutaneous adipose tissue, skeletal muscle, and white blood cells. Ten mature Thoroughbred mares received an insulin infusion that elevated plasma insulin concentrations for 6h or an ...
George LA, Staniar WB, Cubitt TA, Treiber KH, Harris PA, Geor RJ.To characterize the effects of pregnancy on insulin sensitivity (SI) and glucose dynamics in pasture-maintained mares fed supplemental feeds of differing energy composition. Methods: Pregnant (n = 22) and nonpregnant (10) healthy Thoroughbred mares. Methods: Pregnant and nonpregnant mares underwent frequently sampled intravenous glucose tolerance tests at 2 times (period 1, 25 to 31 weeks of gestation; period 2, 47 weeks of gestation). Following period 1 measurements, mares were provided a high-starch (HS; 39% starch) or high-fat and -fiber (14% fat and 70% fiber) supplemental feed. From a sub...
Wearn JM, Crisman MV, Davis JL, Geor RJ, Hodgson DR, Suagee JK, Ashraf-Khorassani M, McCutcheon LJ.Pioglitazone is a thiazolidinedione class of antidiabetic agent with proven efficacy in increasing insulin sensitivity in humans with noninsulin-dependent diabetes mellitus, a syndrome of insulin resistance sharing similarities with equine metabolic syndrome. The purpose of this study was to determine the pharmacokinetics of pioglitazone in adult horses following multiple oral dose administration. Pioglitazone hydrochloride (1 mg/kg) was administered orally for 11 doses at 24-h intervals, and plasma samples were collected. Initially, a pilot study was performed using one horse; and thereafter ...
Han JH, McKenzie HC, McCutcheon LJ, Geor RJ.To investigate the effects of a continuous rate infusion (CRI) of dextrose solution or dextrose solution and insulin on glucose and insulin concentrations in healthy and endotoxin-exposed horses. Methods: 9 adult mares. Methods: During phase 1, treatments consisted of saline (0.9% NaCl) solution (control group; n = 4) or 20% dextrose solution (group 1; 4) administered IV as a 360-minute CRI. During phase 2, treatments consisted of 360-minute CRIs of 20% dextrose solution and insulin administered simultaneously at 367.6 mg/kg/h (30 kcal/kg/d) and 0.07 U/kg/h, respectively, in healthy horses (gr...
Kuhl J, Winterhoff N, Wulf M, Schweigert FJ, Schwendenwein I, Bruckmaier RM, Aurich JE, Kutzer P, Aurich C.Many foals develop diarrhoea within the first two weeks of life which has been suggested to coincide with postpartum oestrus in their dams. To analyse the pathogenesis of this diarrhoea we have determined faecal bacteria in foals and their dams (n=30 each), and serum IGF-1 and γ-globulins for 6 weeks after birth. In addition, effects of β-carotene supplementation to mares (group 1: 1000 mg/day, n=15, group 2: control, n=15) on diarrhoea in foals were studied. Diarrhoea occurred in 92 and 79% of foals in groups 1 and 2, respectively, but was not correlated with oestrus in mares. Beta-carotene...
de Laat MA, van Eps AW, McGowan CM, Sillence MN, Pollitt CC.Laminitis has many triggers and comparing the histopathology of lesions induced by different causes may help to establish whether a common mechanism or multiple pathologies are involved. The aim of this study was to describe the microscopical lesions and to quantify morphometric changes in the lamellae of horses with insulin-induced (n=4) and oligofructose (OF)-induced laminitis (n=4) compared with normal controls (n=4). Archived lamellar samples collected during two previous studies were used. Laminitis was induced within 48 h in standardbred horses with either a euglycaemic, hyperinsulinaemi...
Venugopal CS, Eades S, Holmes EP, Beadle RE.One of the causes of equine laminitis is hyperinsulinaemia, which may be associated with endothelial dysfunction and insulin resistance of vessels. Objective: Insulin resistance can be induced in palmar digital vessels by continued exposure to insulin in vitro. The objective was to evaluate this in vitro model for future studies. Methods: Palmar digital vessel segments were collected immediately after euthanasia from horses with normal insulin/glucose blood values. Four arterial and 4 venous rings (3 mm wide) were prepared and each ring mounted in a tissue bath, containing Tyrode's solution at...
Stewart AJ.Magnesium (Mg) is an essential macroelement that is required for cellular energy-dependent reactions involving adenosine triphosphate and for the regulation of calcium channel function. Subclinical hypomagnesemia is common in critically ill humans and animals and increases the severity of the systemic inflammatory response syndrome; worsens the systemic response to endotoxins; and can lead to ileus, cardiac arrhythmias, refractory hypokalemia, and hypocalcemia. This article discusses the clinical signs, consequences, and treatment of hypomagnesemia in horses and describes the association of Mg...
Frank N.The concept of an equine metabolic syndrome (EMS) was first proposed in 2002. This concept has developed over time, and EMS was recently described in a consensus statement released by the American College of Veterinary Internal Medicine. In human medicine, metabolic syndrome (MetS) refers to a set of risk factors that predict the risk of cardiovascular disease, including obesity, glucose intolerance and insulin resistance (IR), dyslipidemia, microalbuminuria, and hypertension. EMS shares some of the features of MetS, including increased adiposity, hyperinsulinemia, IR, but differs in that lami...
McKenzie HC.Hyperlipidemia is the presence of elevated lipid concentrations in the blood and is associated with periods of negative energy balance and physiologic stress. In increased concentrations, circulating lipids typically occur in the triglyceride form, which may interfere with numerous normal physiologic functions, particularly by reducing insulin sensitivity. Although the hyperlipidemia risk is greatest in ponies, miniature horses, and donkeys, all equids are at risk if they are in a situation involving negative energy balance. The sedentary lifestyle of many modern horses and the frequent feedin...
Tinworth KD, Boston RC, Harris PA, Sillence MN, Raidal SL, Noble GK.Metformin may be an effective therapeutic option for insulin-resistant (I-R) horses/ponies because, in humans, it reportedly enhances insulin sensitivity (SI) of peripheral tissues without stimulating insulin secretion. To determine the effect of metformin on insulin and glucose dynamics in I-R ponies, six ponies were studied in a cross-over design by Minimal Model analysis of a frequently-sampled intravenous glucose tolerance test (FSIGT). Metformin was administered at 15 mg/kg bodyweight (BW), orally, twice-daily, for 21 days to the metformin-treated group. The control group received a place...
Bridges TS, Davidson TR, Chamberlain CS, Geisert RD, Spicer LJ.The objective of the present study was to evaluate changes in equine follicular fluid insulin-like growth factor binding protein (IGFBP) proteolytic activity as well as steroid, IGF, and IGFBP concentrations during follicular development in the mare. Mares (n = 14) were classified as either in the follicular phase (n = 8) or luteal phase (n = 6). Follicles (n = 92) were categorized as small (6 to 15 mm; n = 54), medium (16 to 25 mm; n = 23), or large (> 25 mm; n = 15), and follicular fluid was collected. Estradiol and androstenedione levels in follicular fluid were greater (P < 0.05), an...
Silver M, Fowden AL.In the present study, ten insulin challenge tests were carried out on nine chronically catheterized fetal foals between 253 and 314 days gestation (term > 320 days). Changes in fetal plasma concentrations of glucose, catecholamines, cortisol, ACTH, free fatty acid (FFA) and lactate were measured before and after a bolus dose of insulin (0.5-2.0 u/kg I.V.). Fetal blood gases, pH, haemoglobin levels and heart rate were measured throughout the 2-3h experimental period. The fetuses fell into two distinct groups on the basis of proximity to delivery and basal plasma cortisol and catecholamine level...
Verwilghen DR, Vanderheyden L, Franck T, Busoni V, Enzerink E, Gangl M, Lejeune JP, van Galen G, Grulke S, Serteyn D.Developmental osteochondral lesions are often encountered in the equine population and are a major cause of lameness. Different growth factors that act systemically as well as locally regulate the growth of cartilage. Among them is Insulin-like Growth Factor I that has been demonstrated to promote chondrocyte growth and differentiation and that has been shown to influence cartilage repair. The aims of this study were to investigate differences in circulating plasma levels of Insulin-like Growth Factor-I in post-pubescent horses affected with developmental osteochondral lesions compared to unaf...
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...
Garcia MC, Beech J.Intravenous glucose tolerance testing (0.5 g/kg of body weight) was done on 2 groups of healthy horses maintained with hay (group 1, n = 5) and with hay plus grain supplementation (group 2, n = 5) and on a group of horses with clinically diagnosed pituitary adenoma (group 3, n = 10). Healthy horses showed an immediate increase of plasma glucose concentration after the IV glucose injection, with return of values to base line in 1 hour. Group 3 horses showed resting hyperglycemia and a delayed return of glucose values to base line (3 hours). Group 3 horses showed resting hyperinsulinemia and a f...
De La Corte FD, Valberg SJ, MacLeay JM, Williamson SE, Mickelson JR.To determine whether excessive glycogen accumulation in skeletal muscle of Quarter Horses with polysaccharide storage myopathy (PSSM) is a result of enhanced cellular uptake of glucose. Methods: 6 horses with PSSM and 10 healthy (control) horses. Methods: Intravenous glucose tolerance tests (IVGTT), oral glucose tolerance tests (OGTT), and modified insulin tolerance tests (MITT) were performed. Plasma glucose and insulin concentrations were measured in blood samples collected before and for up to 8 hours after glucose or insulin administration. Results: Peak glucose concentrations during IVGTT...
Cartmill JA, Thompson DL, Gentry LR, Pruett HE, Johnson CA.In experiment 1, nine light horse geldings (three 3 x 3 Latin squares) received dexamethasone (DEX; 125 microg/kg BW, i.m.), glucose (0.2 g/kg BW, i.v.), or nothing (control) once per day for 4 days. DEX increased (P < 0.001) glucose, insulin, and leptin concentrations and resulted in a delayed increase (P < 0.001) in IGF-I concentrations. In experiment 2, mares were similarly treated with DEX (n = 6) or vehicle (n = 6). DEX again increased (P < 0.01) glucose, insulin, and leptin concentrations; the delayed elevation in IGF-I concentrations occurred on day 10, 12, and 19, relative to ...
Vervuert I, Coenen M, Bothe C.This study was conducted to evaluate the effects of different oat processing techniques on the plasma glucose and insulin response in horses. In a cross-over design, six horses (ages 4-15 years, mean body weight+/-SD: 450+/-37 kg) were fed in random order: untreated oats, finely ground, steam-flaked and popped oats. The total oat intake varied between 1.05-1.5 kg/day, and the amount of diet was adjusted to a starch content of 630 g starch per day and horse (1.2-1.5 g starch/kg BW/day). During the stabilization period of 10 days, horses additionally received 6 kg grass hay. Following this adapt...
Matsui A, Ohmura H, Asai Y, Takahashi T, Hiraga A, Okamura K, Tokimura H, Sugino T, Obitsu T, Taniguchi K.In man, muscle protein synthesis is accelerated by administering amino acids (AA) and glucose (Glu), because increased availability of amino acids and increased insulin secretion, is known to have a protein anabolic effect. However, in the horse, the effect on muscle hypertrophy of such nutrition management following exercise is unknown. Objective: To determine the effect of AA and Glu administration following exercise on muscle protein turnover in horses. We hypothesise that administration of AA and Glu after exercise effects muscle hypertrophy in horses, as already shown in man and other ani...
Ross MW, Lowe JE, Cooper BJ, Reimers TJ, Froscher BA.A 12-year-old, 195 kg Shetland pony broodmare had eight seizures between May 29 and August 7, 1979. Plasma glucose levels during three of these seizures were markedly depressed (16, 18 and 19 mg/100 ml). Serum insulin levels were elevated during two of the seizures (86.0 and 97.7 microU/ml). Although a fasting hypoglycemia was not demonstrated, plasma glucose values during a normal day were abnormal; a plasma glucose level of 42 mg/100 ml was noted eight hours post-feeding. Serum insulin values obtained during an oral glucose tolerance test and intravenous glucagon tolerance test were consiste...
Frank N, Andrews FM, Elliott SB, Lew J, Boston RC.Plasma lipid concentrations, lipoprotein composition, and glucose dynamics were measured and compared between mares fed diets containing added water, corn oil (CO), refined rice bran oil (RR), or crude rice bran oil (CR) to test the hypothesis that rice bran oil lowers plasma lipid concentrations, alters lipoprotein composition, and improves insulin sensitivity in mares. Eight healthy adult mares received a basal diet fed at 1.5 times the DE requirement for maintenance and each of the four treatments according to a repeated 4 x 4 Latin square design consisting of four 5-wk feeding periods. Blo...
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)...
Vervuert I, Klein S, Coenen M.A standardised methodology is required for classification of starchy diets. One important question is what feeding status is optimal to describe glycaemic and insulinaemic responses to the respective starchy diet. Four horses were fed, in a randomised order, four different feeding protocols relative to offering hay before or after cracked corn (CC): (i) ad libitum hay for 12 h before feeding CC and ad libitum hay after CC intake for 9 h (+CC+), (ii) ad libitum hay for 12 h before feeding CC and no hay after CC intake for 9 h (+CC-), (iii) feed restriction for 12 h before feeding CC and ad libi...
Porter RM, Akers RM, Howard RD, Forsten-Williams K.Alginate hydrogel culture has been shown to reestablish chondrocytic phenotype following monolayer expansion; however, previous studies have not adequately addressed how culture conditions affect the signaling systems responsible for chondrocyte metabolic activity. Here we investigate whether chondrocyte culture history influences the insulin-like growth factor-I (IGF-I) signaling system and its regulation by interleukin-1 (IL-1). Articular chondrocytes (ACs) from equine stifle joints were expanded by serial passage and were either encapsulated in alginate beads or maintained in monolayer cult...
Sticker LS, Thompson DL, Bunting LD, Fernandez JM, DePew CL, Nadal MR.Twelve light horse mares were fed a control diet that provided 100% of their maintenance protein and energy requirements for 7 d and were then either continued on the control diet or totally deprived of feed (with access to water) for 3 d . Plasma samples were drawn twice daily throughout the experiment, at 15-min intervals for 9 h beginning 45 h after feed removal, and at 10-min intervals around an exercise bout beginning 73 h after feed removal. Feed deprivation increased (P < or = .06) whole blood beta-hydroxybutyrate and plasma NEFA, urea N, L-lactate, and glucagon concentrations, decrease...
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...
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...
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...
Jose-Cunilleras E, Hinchcliff KW, Sams RA, Devor ST, Linderman JK.In a randomized, balanced, crossover study each of six fit, adult horses ran on a treadmill at 50% of maximal rate of oxygen consumption for 60 min after being denied access to food for 18 h and then 1) fed corn (51.4 kJ/kg digestible energy), or 2) fed an isocaloric amount of alfalfa 2-3 h before exercise, or 3) not fed before exercise. Feeding corn, compared with fasting, resulted in higher plasma glucose and serum insulin and lower serum nonesterified fatty acid concentrations before exercise (P < 0.05) and in lower plasma glucose, serum glycerol, and serum nonesterified fatty acid conce...
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...
Tóth F, Frank N, Geor RJ, Boston RC.To investigate the effects of dexamethasone or levothyroxine sodium on endotoxin-induced alterations in glucose and insulin dynamics. Methods: 24 horses. Methods: Horses were randomly allocated to 3 treatment groups and received 48 mg of levothyroxine mixed with 200 g of oats, 20 mg of dexamethasone plus oats, or oats alone (control) for 15 days, followed by IV infusion of lipopolysaccharide (20 ng/kg) while individually housed in stalls. Frequently sampled IV glucose tolerance tests were performed prior to pretreatment, after pretreatment, and 20 hours after lipopolysaccharide administration....
Ragno VM, Klein CD, Sereda NS, Uehlinger FD, Zello GA, Robinson KA, Montgomery JB.In human metabolic syndrome and type II diabetes, methylglyoxal (MG), D-lactate, and several cytokines have been recognized as biomarkers of important metabolic and inflammatory processes. Equine metabolic syndrome (EMS) shares many similarities with these human counterparts. The objectives of this cross-sectional study were to compare body condition score (BCS), cresty neck score (CNS), resting insulin, MG, D-lactate, L-lactate, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) between horses with and without insulin dysregulation, as clas...
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 ...
Schmidt O, Deegen E, Fuhrmann H, Dühlmeier R, Sallmann HP.The aim of this study was to investigate the influence of a fat-supplemented diet compared with a carbohydrate diet on the lipid metabolism and the enteroinsular axis of Shetland ponies. The 'crossover' experiment was divided into two parts: in the first 10 weeks the diets comprised the correct number of calories according to requirements and in the following 10 weeks they were hypercaloric, in order to check the effect of a different energy content of the diets. Feeding the fat-enriched diet, independently of its energy content, led to a significant decrease in plasma triglycerides, associate...
Smyth GB, Young DW, Hammond LS.Gastrin is the only hormone known to stimulate secretion of hydrochloric acid. It also has trophic effects on specific parts of the mucosa of the gastrointestinal tract. Using radioimmunoassay techniques, postprandial serum gastrin and insulin concentrations were measured in six adult horses to establish effects of different diets on gastrin concentrations. Insulin concentrations were measured to provide support to the patterns of gastrin secretion because patterns of insulin secretion were already known. The horses were fed coastal bermuda hay, or twice daily 5 kg of a complete pelleted ratio...
Aguiar FLN, Gastal GDA, Ishak GM, Gastal MO, Teixeira DIA, Feugang JM, Figueiredo JR, Gastal EL.The effect of FSH supplementation on an enriched cultured medium containing insulin (10 ng/mL) and EGF (50 ng/mL) was investigated on in vitro culture of equine ovarian biopsy tissue. Ovarian tissue fragments were collected from mares (n = 10) and distributed in the following treatments: noncultured control, cultured control, and cultured + FSH. Both treated groups were cultured for 7 or 15 days. The end points evaluated were: follicular morphology, estradiol levels in the culture medium, fluorescence intensity for TUNEL, EGFR and Ki-67 detection, and gene expression of GDF-9, BMP-15, a...
Cartmill JA, Thompson DL, Storer WA, Crowley JC, Huff NK, Waller CA.Three experiments tested the hypotheses that daily cortisol rhythm, feeding time, and/or insulin infusion affect(s) leptin secretion in stallions. Ten mature stallions received ad libitum hay and water and were fed a grain concentrate once daily at 0700. In Exp. 1, stallions received either a single injection of dexamethasone (125 microg/kg BW i.m.; n = 5) or vehicle (controls; n = 5) at 0700 on d -1. Starting 24 h later, blood samples were collected every 2 h for 36 h via jugular venipuncture. Cortisol in control stallions varied (P < 0.01) with time, with a morning peak and evening nadir;...
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...
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...
Williams CA, Kronfeld DS, Staniar WB, Harris PA.Plasma concentrations of glucose and insulin following a meal were compared in twelve Thoroughbred mares fed a pelleted concentrate (PC), a traditional sweet feed high in sugar and starch (SS), or a feed high in fat and fiber (FF). The feeds had similar DE and CP but differed in fat (19, 32, and 166 g/kg DM, respectively), NDF (199, 185, and 369 g/kg DM, respectively) and nonstructural carbohydrates (574, 645, and 247 g/kg, respectively). Mares were randomly assigned to two groups balanced for foaling date and weight. All mares received PC in late gestation; then, after foaling, one group was ...
