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.
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...
Langner K, Blaue D, Schedlbauer C, Starzonek J, Julliand V, Vervuert I.Obesity is a major health concern in many domesticated equids animals since it is related to metabolic abnormalities such as insulin dysregulation, hyperlipidaemia or laminitis. Ponies especially are known as "easy keepers" and are often affected by obesity and its related metabolic disorders. Research in the last decade indicated that the intestinal microbiota may play an important role in the development of obesity, at least in humans. Therefore, the objective of our study was to characterize changes in the faecal microbiota during a two-year weight gain programme which compared ponies and w...
Cunneen A, Wood KA, Mathison K, Herndon AM, Bertin FR.Blood glucose is tightly regulated in horses; however, since hypoglycaemia and hyperglycaemia are associated with poor prognosis, close monitoring is warranted. This study aimed at evaluating a continuous indwelling glucometer (CIG) by comparing performance with a point-of-care glucometer (POC). Ten horses were equipped with CIG and an intravenous catheter. Interstitial glucose concentrations were determined by CIG every 5 min at rest, during insulin-induced hypoglycaemia and dextrose-induced hyperglycaemia, and compared with blood glucose determined by POC. Glucose concentrations were compa...
Zak A, Siwinska N, Elzinga S, Barker VD, Stefaniak T, Schanbacher BJ, Place NJ, Niedzwiedz A, Adams AA.Age, neurodegenerative disorders, and dysfunction of insulin secretion may be correlated with increased systemic concentrations of acute phase markers. Thus, the study aimed to determine the effect of age, pituitary pars intermedia dysfunction (PPID), and insulin dysregulation (ID) associated with PPID, on markers of the acute phase reaction. Twenty-nine mix-breed horses of both sexes were classified into groups: (1) healthy adult controls, (2) healthy non-PPID geriatric horses, (3) PPID ID+ horses, and (4) PPID ID- horses. Whole blood proinflammatory cytokine gene expression and serum concent...
Kritchevsky JE, Muir GS, Leschke DHZ, Hodgson JK, Hess EK, Bertin FR.In metabolically stable horses, alpha-2-agonists suppress insulin secretion with transient hyperglycemia and rebound hyperinsulinemia. In horses with insulin dysregulation (ID), the effect of alpha-2-agonists has not been investigated; however, both the alpha-2-agonist-induced suppression of insulin secretion and rebound hyperinsulinemia could have clinical relevance. Objective: In horses with ID, alpha-2-agonists will alter insulin and glucose dynamics. Methods: Seven horses with ID and 7 control horses. Methods: In this randomized crossover study, xylazine hydrochloride (1.1 mg/kg) or detomi...
Zak A, Siwinska N, Elzinga S, Barker VD, Stefaniak T, Schanbacher BJ, Place NJ, Niedzwiedz A, Adams AA.Obesity and metabolic disorders are associated with systemic low-grade chronic inflammation, both in humans and animals. The aim of the study is to assess the effects of obesity and hyperinsulinemia on individual components of the acute-phase reaction in equine metabolic syndrome (EMS) horses. Eight mixed-breed EMS and six control, age-matched horses of both sexes were included in the study. Animals were classified as EMS or control based on the assessment of BCS, cresty neck score, and basal insulin >50 μU/mL and/or insulin responses to the oral sugar test (OST) >60 μU/mL. Peripheral ...
Hansen TL, Rankins EM, Bobel JM, McKinney M, Hackmann TJ, Warren LK.In humans, the consumption of soluble fibers reduces glycemic response after a meal. We hypothesized high soluble fiber diets would reduce and delay postprandial glucose and insulin responses in horses. In a 4 × 4 Latin square design experiment, four Quarter Horse geldings were adapted to diets containing orchardgrass hay (ORCH) or ORCH with 1 of 3 treatment ingredients: molassed sugar beet pulp (BEET), almond hulls (HULL), or steam-crimped oats (OATS). Blood was serially sampled for 6 hours after feeding 0.15% body weight (BW) of the treatment ingredient (meal test) or 1.1 g starch/kg BW ...
Stokes SM, Bertin FR, Stefanovski D, Belknap JK, Medina-Torres CE, Pollitt CC, van Eps AW.Hyperinsulinaemia is associated with the development of endocrinopathic laminitis; however, the mechanisms remain unclear. Objective: Evaluate the effects of hyperinsulinaemia on lamellar energy metabolism and perfusion during laminitis development. Methods: In vivo experiment. Methods: Eight Standardbred horses were instrumented with a microdialysis probe in the lamellae of a forelimb. A 24 hours baseline period (BASELINE) was followed by 48 hours of a continuous euglycaemic hyperinsulinaemic clamp (EHC) from 24 to 72 hours (CLAMP). Microdialysate was collected every 6 hours and analysed ...
Van Den Wollenberg L, Vandendriessche V, van Maanen K, Counotte GHM.Straightforward testing procedures to enable the diagnosis of insulin dysregulation (ID) in horses that are suitable for use in daily veterinary practice are needed because of the risk that ID could result in laminitis. In our study (that included 90 horses), we compared the proportion of horses classified as ID-positive, ID-suspect, and ID-not diagnosed according to the basal insulin concentration (BIC) with the proportion of horses classified as ID-positive or ID-negative according to a practical and feasible version of an oral sugar test (OST). Furthermore, BIC, basal glucose concentration,...
Cash CM, Fitzgerald DM, Spence RJ, de Laat MA.Equine metabolic syndrome (EMS) describes a group of risk factors, including obesity and insulin dysregulation (hyperinsulinemia and/or insulin resistance), that can lead to the development of the debilitating hoof disease laminitis. Although the underlying mechanisms of EMS are not fully understood, a genetic component has been reported, and an 11 guanine polymorphism located at the FAM174A gene has been identified as a risk locus for the syndrome in Arabian horses. To examine associations between the FAM174A risk allele and the clinical signs of EMS, the allele was examined in an Australian ...
Pennington PM, Splan RK, Jacobs RD, Chen Y, Singh RP, Li Y, Gucek M, Wagner AL, Freeman EW, Pukazhenthi BS.Insulin resistance (IR) is characterized by an increase in biomarkers of systemic inflammation and susceptibility to laminitis in horses. Impacts on reproduction include a lengthened interovulatory period in horses. Dietary omega-3 (docosahexaenoic acid [DHA]) promotes anti-inflammatory processes, has been implicated in health benefits, and can reduce cytokine secretion. This preliminary study investigated the impact of IR as well as the influence of dietary supplementation (DHA) on the uterine fluid proteome in early pregnant horses. Mares were artificially inseminated; uterine fluid and embr...
Manfredi JM, Stapley ED, Nadeau JA, Nash D.High insulin concentrations are a common clinical feature of equine metabolic syndrome (EMS) and insulin dysregulation. Hyperinsulinemia can induce laminitis, so reduction of insulin concentrations in response to an oral challenge should decrease risk. In human studies, diets containing a polyphenol (resveratrol) led to improvements in insulin sensitivity. In rodents, the addition of leucine to a resveratrol supplement caused a decrease in the amount of resveratrol needed to achieve a clinical effect. We hypothesize a supplementation with a low dose of a synergistic polyphenol and amino acid b...
Gehlen H, Twickel S, Stöckle S, Weber C, Bartmann CP.Pituitary pars intermedia dysfunction is the most prevalent endocrine disease in horses. Although donkeys and mules may also be affected, only a few data have been published. Reference values for diagnostic parameters, such as adrenocorticotropic hormone (ACTH), are especially scarce or even lacking. Therefore, in the present study, available data from the literature have been verified and completed to facilitate a reliable diagnosis. Clinical inspections and haematological and biochemical examinations were carried out four times in a three-month interval (February to November) in 44 donkeys a...
Van Weyenberg S, Hesta M, Buyse J, Janssens GP.In nine initially obese ponies, a weekly weight loss according to 1% of their ideal body weight was evaluated for its impact on insulin sensitivity and metabolic profile. Weight loss was obtained solely through energy restriction, initially at 70% of maintenance energy requirements, but to maintain constant weight loss, feed amount had to be decreased to 50% and 35% of maintenance energy requirement during the course of the trial. An oral glucose tolerance test (OGTT) was performed at weeks 0, 10 and 17. Fasted blood samples were taken on weeks 0, 3, 10, 17 for analysis of triglycerides (TG), ...
Karikoski NP, Patterson-Kane JC, Asplin KE, McGowan TW, McNutt M, Singer ER, McGowan CM.To determine cellular changes associated with secondary epidermal laminae (SEL) in forefeet and hind feet of ponies with insulin-induced laminitis. Methods: 8 ponies. Methods: Laminitis was induced in 4 ponies by IV administration of insulin and glucose; 4 control ponies received saline (0.9% NaCl) solution IV. Laminar tissue samples obtained from the dorsal aspects of the hooves were histologically evaluated. Primary epidermal lamina (PEL) length and width and SEL length, width, and angle were determined. Numbers of epidermal cell nuclei per micrometer and per total length of SEL and numbers ...
Bröjer J, Lindåse S, Hedenskog J, Alvarsson K, Nostell K.The increasing number of horses diagnosed with insulin resistance (IR) and the suggested link between IR and laminitis has highlighted the need to accurately diagnose IR in clinical practice. Objective: The aim of the study was to evaluate the repeatability of the combined glucose-insulin tolerance test (CGIT) as well as to determine the effect of 2 different breeds and the effect of a stressor on the test results. Methods: Clinically normal horses, 9 Standardbred horses and 9 Icelandic horses. Methods: Prospective clinical nonrandomized trial. The CGIT was performed on all horses on 2 occasio...
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...
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...
Dunbar LK, Mielnicki KA, Dembek KA, Toribio RE, Burns TA.Several tests have been evaluated in horses for quantifying insulin dysregulation to support a diagnosis of equine metabolic syndrome. Comparing the performance of these tests in the same horses will provide clarification of their accuracy in the diagnosis of equine insulin dysregulation. Objective: The aim of this study was to evaluate the agreement between basal serum insulin concentrations (BIC), the oral sugar test (OST), the combined glucose-insulin test (CGIT), and the frequently sampled insulin-modified intravenous glucose tolerance test (FSIGTT). Methods: Twelve healthy, light-breed ho...
Fortier LA, Kornatowski MA, Mohammed HO, Jordan MT, O'Cain LC, Stevens WB.Structural changes in articular cartilage associated with the ageing process require definition for investigators performing developmental and age-related studies, for which information is lacking. Objective: To 1) determine the onset and end of puberty as defined by serum insulin like growth factor (IGF-I) and IGF-binding protein-3 (IGFBP-3) concentrations and 2) correlate articular-epiphyseal cartilage complex structural changes with the onset and end of puberty. Methods: IGF-I and IGFBP-3 were measured in serum samples from normal female and male horses age 9-715 days to determine peak and ...
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...
Kenéz Á, Warnken T, Feige K, Huber K.Insulin dysregulation in horses is a metabolic condition defined by high insulin concentrations in the blood and peripheral insulin resistance. This hyperinsulinemia is often associated with severe damage in the hooves, resulting in laminitis. However, we currently lack detailed information regarding the potential involvement of particular metabolic pathways in pathophysiological causes and consequences of equine insulin dysregulation. This study aimed to assess the dynamic metabolic responses given to an oral glucose test (OGT) in insulin-sensitive and insulin-dysregulated horses by a targete...
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...
Mendoza FJ, Toribio RE, Perez-Ecija A.The donkey evolved under harsh and arid environmental conditions, developing unique energy-efficiency traits, with an efficiency to rapidly mobilize fat in situations of increased energy demands or when food is scarce. This evolution has led to an inherent predisposition of donkeys to obesity, dyslipidemias, insulin dysregulation/metabolic syndrome, pituitary pars intermedia dysfunction, and endocrinopathic laminitis. Marked differences have been described in hormone dynamics and testing protocols for the diagnosis of these endocrine and metabolic diseases in donkeys compared with horses, unde...
van Eps AW, Burns TA.Laminitis is a consequence of primary disease processes elsewhere in the body. The key pathophysiologic events are insulin dysregulation in endocrinopathic laminitis, ischemia in supporting limb laminitis, and inflammation in sepsis-related laminitis. These apparently disparate mechanisms converge to cause lamellar attachment failure through epithelial cell adhesion loss and stretch, possibly mediated by common growth factor signaling pathways. Tissue damage through mechanical distraction, inflammation, pain, and a proliferative epithelial healing response are features of acute laminitis regar...
Love S.In the horse, adenomata of the pairs intermedia of the pituitary gland have been associated with the distinct clinical entity of Cushing's disease which arises largely as a result of excessive secretion of adrenocorticotropin (ACTH) or other proopiomelanocortin (POMC) peptides. Pars intermedia peptide secretion is under dopaminergic control and compounds such as pergolide or bromocriptine, which are dopamine agonists, can palliate the clinical signs. A variety of endocrinological abnormalities, relevant to both pathogenesis and diagnosis, may be demonstrated in equine Cushing's disease, includ...
Jeffcott LB, Henson FM.The importance of osteochondrosis (dyschondroplasia) to the horse industry has been well documented since it was first recorded 50 years ago. The condition is known to be multifactorial in origin, arising from focal failure of endochondral ossification at predilection sites in articular/epiphyseal growth cartilage, but specific information on its aetiopathogenesis is sparse. This paper reviews the current knowledge of growth cartilage metabolism and the process of normal endochondral ossification in the horse. It highlights the localization of various protein products of chondrocytes and the d...
Mizukami H, Suzuki T, Nambo Y, Ishimaru M, Naito H, Korosue K, Akiyama K, Miyata K, Yamanobe A, Nagaoka K, Watanabe G, Taya K.Development and endocrine changes in Thoroughbreds colts and fillies were compared between those reared at two facilities of the Japan Racing Association, the Hidaka Training and Research Center (Hidaka) and Miyazaki Yearling Training Farm (Miyazaki). Thoroughbred colts and fillies born in Japan between 2003 and 2010 were used. Each colt group and filly group was divided into 2 groups, respectively, and raised in Hidaka or Miyazaki for 7 months from September at 1 year old to April at 2 years old. For the growth parameters, the body weight, height at withers, and girth and cannon circumference...
Bertin FR, Sojka-Kritchevsky JE.Equine insulin resistance is important because of its association with laminitis. The insulin-response test is described to diagnose insulin resistance in clinical settings. Practitioners may be reluctant to perform this test because of the time needed for the test and the fear of inducing hypoglycemia. The objective of the study was to compare a 2-step insulin-response test with a complete insulin-response test. A complete insulin-response test was performed on 6 insulin-resistant horses and 6 controls. A 2-step insulin-response test consisting of an intravenous injection of 0.1 IU/kg human i...
Ribeiro WP, Valberg SJ, Pagan JD, Gustavsson BE.The effect of dietary starch and fat content on serum creatine kinase (CK) activity and substrate availability was evaluated in 4 mares of Quarter Horse-related breeds with polysaccharide storage myopathy (PSSM). Four isocaloric diets ranging in digestible energy (DE) from 21.2% (diet A), 14.8% (B), 8.4% (C), to 3.9% (D) for starch, and 7.2% DE (diet A), 9.9% (B), to 12.7% DE (diet C and D) for fat were fed for 6-week periods (4 weeks with exercise) using a 4 X 4 Latin square design. Postprandial glucose and insulin responses were measured, and 4 hours postexercise, serum CK activity, glucose,...
Semevolos SA, Nixon AJ, Brower-Toland BD.To determine molecular changes in the expression of insulin-like growth factor-I (IGF-I) and transforming growth factor-beta1 (TGF-beta1) in horses with osteochondrosis, and to characterize expression of matrix aggrecan and collagen types I, II, and X in articular cartilage of affected joints. Methods: Articular cartilage from affected stifle or shoulder joints of 11 horses with naturally acquired osteochondrosis and corresponding joints of 11 clinically normal horses. Methods: Harvested specimens were snap frozen in liquid nitrogen, and total RNA was isolated. Specimens were fixed in 4% paraf...
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...
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...
Robles M, Nouveau E, Gautier C, Mendoza L, Dubois C, Dahirel M, Lagofun B, Aubrière MC, Lejeune JP, Caudron I, Guenon I, Viguié C, Wimel L....Obesity is a growing concern in horses. The effects of maternal obesity on maternal metabolism and low-grade inflammation during pregnancy, as well as offspring growth, metabolism, low-grade inflammation, testicular maturation and osteochondrotic lesions until 18 months of age were investigated. Twenty-four mares were used and separated into two groups at insemination according to body condition score (BCS): Normal (N, n = 10, BCS ≤4) and Obese (O, n = 14, BCS ≥4.25). BCS and plasma glucose, insulin, triglyceride, urea, non-esterified fatty acid, serum amyloid A (SAA), leptin and adiponect...
Borer KE, Bailey SR, Menzies-Gow NJ, Harris PA, Elliott J.Identification of ponies (Equus caballus) at increased risk of pasture-associated laminitis would aid in the prevention of the disease. Insulin resistance has been associated with laminitis and could be used to identify susceptible individuals. Insulin resistance may be diagnosed by feeding supplementary water-soluble carbohydrate (WSC) and measuring blood glucose and insulin concentrations. The aim of this study was to assess the glycemic and insulinemic responses of 7 normal (NP) and 5 previously laminitic (PLP), mixed breed, native UK ponies fed glucose, fructose, and inulin [1 g/(kg·d) fo...
de Laat MA, Kyaw-Tanner MT, Sillence MN, McGowan CM, Pollitt CC.Advanced glycation endproducts (AGEs) have been implicated in the pathogenesis of cancer, inflammatory conditions and diabetic complications. An interaction of AGEs with their receptor (RAGE) results in increased release of pro-inflammatory cytokines and reactive oxygen species (ROS), causing damage to susceptible tissues. Laminitis, a debilitating foot condition of horses, occurs in association with endocrine dysfunction and the potential involvement of AGE and RAGE in the pathogenesis of the disease has not been previously investigated. Glucose transport in lamellar tissue is thought to be l...
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...
Tóth F, Frank N, Elliott SB, Geor RJ, Boston RC.To evaluate the effects of endotoxin administered IV on glucose and insulin dynamics in horses. Methods: 16 healthy adult mares. Methods: Each week of a 2-week randomized crossover study, each horse received an IV injection (duration, 30 minutes) of Escherichia coli O55:B5 lipopolysaccharide (LPS) in 60 mL of sterile saline (0.9% NaCl) solution (20 ng/kg) or sterile saline solution alone (control treatment). Frequently sampled IV glucose tolerance test procedures were performed at 24 hours before (baseline) and 24 and 48 hours after injection; glucose and insulin dynamics were assessed via min...
Reimers TJ, Lamb SV, Bartlett SA, Matamoros RA, Cowan RG, Engle JS.Veterinary diagnostic endocrinology laboratories frequently receive hemolyzed plasma, serum, or blood samples for hormone analyses. However, except for the previously reported harm done by hemolysis to canine insulin, effects of hemolysis on quantification of other clinically important hormones are unknown. Therefore, these studies were designed to evaluate effects of hemolysis on radioimmunoassay of thyroxine, 3,5,3'-triiodothyronine, progesterone, testosterone, estradiol, cortisol, and insulin in equine, bovine, and canine plasma. In the first experiment, hormones were measured in plasma obt...
Banse HE, McCann J, Yang F, Wagg C, McFarlane D.Diagnosis of equine hyperinsulinemia requires an accurate method for quantification of equine insulin concentrations. The objectives of the current study were to compare 2 commercially available techniques for measurement of equine insulin, the radioimmunoassay (RIA) and chemiluminescent immunoassay (CIA). Recovery was poor for both assays, but worse for the CIA. Serial dilution of a high endogenous insulin sample yielded better linearity for the RIA ( r = 0.99, P < 0.001) than the CIA ( r = 0.92, P = 0.009). Bland-Altman analysis indicated that the CIA was, on average, 91 pmol/l higher tha...
McFarlane D.Despite there being only 2 common endocrine diseases in horses, pituitary pars intermedia dysfunction (PPID) and equine metabolic syndrome (EMS), diagnosis is still confusing. Failing to consider horse factors and treating based on laboratory results only have caused many animals to receive lifelong drug treatment unnecessarily. Increased plasma ACTH, baseline or TRH stimulated, supports a diagnosis of PPID; however, breed, age, thriftiness, illness, coat color, geography, diet, and season also affect ACTH concentration. Insulin dysregulation, the hallmark of EMS, can result from insulin resis...
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,...
