Distribution and sequence analysis of the melanocortin 2 receptor in horses and ponies.

The melanocortin 2 receptor (MC2R) has relevance to equine pituitary pars intermedia dysfunction (PPID), as it is the primary binding site for ACTH, which circulates at elevated concentrations in animals affected by PPID. Despite this, little is known about MC2R in equine species. The overall aim of this investigation was to determine MC2R mRNA expression in tissues relevant to PPID in healthy horses and to examine the MC2R gene sequence in a cohort of horses and ponies with and without PPID.

Effect of short-term dopamine reduction on insulin sensitivity and post-prandial insulin and glucose responses in Standardbred horses.

The role of dopamine in the regulation of insulin secretion in horses is poorly understood and requires further investigation. Pituitary pars intermedia dysfunction (PPID) is associated with decreased activity of dopaminergic neurons which normally suppress peptide hormone secretion from the pituitary pars intermedia. A high proportion of horses with PPID also have insulin dysregulation (ID), characterised by post-prandial hyperinsulinaemia and/or tissue insulin resistance, which are risk factors for the development of laminitis.

Physiological and metabolic effects of short-term dopamine reduction in healthy horses using a tyrosine hydroxylase inhibitor (alpha-methyl-para-tyrosine).

Alpha-methyl-para-tyrosine (AMPT) is a reversible inhibitor of tyrosine hydroxylase, the rate-limiting enzyme in catecholamine synthesis. This study aimed to determine whether AMPT could reduce dopamine concentrations in horses. Six healthy adult Standardbred geldings were administered AMPT (40 mg/kg BW, orally) or placebo in a randomised crossover study design.

Evidence for dopamine production and distribution of dopamine D2 receptors in the equine gastrointestinal mucosa and pancreas.

Insulin dysregulation in horses is characterised by hyperinsulinaemia and/or tissue insulin resistance and is associated with increased risk of laminitis. There is growing evidence in other species that dopamine attenuates insulin release from the pancreas; however, this has yet to be examined in horses. The present study aimed to identify whether there are cells capable of producing or responding to dopamine within the equine gastrointestinal mucosa and pancreas.

Expression of the GCG gene and secretion of active glucagon-like peptide-1 varies along the length of intestinal tract in horses.

Background: Active glucagon-like peptide-1 (aGLP-1) has been implicated in the pathogenesis of equine insulin dysregulation (ID), but its role is unclear. Cleavage of proglucagon (coded by the GCG gene) produces aGLP-1 in enteral L cells.

Objectives: The aim in vivo was to examine the sequence of the exons of GCG in horses with and without ID, where aGLP-1 was higher in the group with ID.

Associations between feeding and glucagon-like peptide-2 in healthy ponies.

Background: Gastrointestinal peptides, such as glucagon-like peptide-2 (GLP-2), could play a direct role in the development of equine hyperinsulinaemia.

Objectives: To describe the secretory pattern of endogenous GLP-2 over 24 h in healthy ponies and determine whether oral administration of a synthetic GLP-2 peptide increases blood glucose or insulin responses to feeding.

Study Design: A cohort study followed by a randomised, controlled, cross-over study.

Equine metabolic syndrome: Role of the enteroinsular axis in the insulin response to oral carbohydrate.

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).

Carbohydrate pellets to assess insulin dysregulation in horses.

Background: A glycemic challenge test is used for the diagnosis of insulin dysregulation (ID) in horses and ponies. Different forms of the test exist where the administrative route and dose of glucose vary, which makes interpretation of results challenging.

Hypothesis/objectives: To evaluate the palatability of, and blood glucose and insulin responses to, carbohydrate pellets fed as an oral glucose test (OGT), and to establish the diagnostic threshold for ID when using the pellets.

A starch-rich treat affects enteroinsular responses in ponies.

Objective: To determine the effect of a starch-rich treat, added to the daily diet of ponies for 10 days, on enteroinsular responses to meal consumption.

Animals: 10 mixed-breed adult ponies owned by Queensland University of Technology were used in the study. Six ponies were metabolically healthy, and 4 were insulin dysregulated at the start of the study, according to the results of an in-feed oral glucose test.

Effects of an anti-IGF-1 receptor monoclonal antibody on laminitis induced by prolonged hyperinsulinaemia in Standardbred horses.

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 euglycaemic-hyperinsulinaemic clamp technique.

Differential Proteomic Expression of Equine Cardiac and Lamellar Tissue During Insulin-Induced Laminitis.

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.

The effect of diet change and insulin dysregulation on the faecal microbiome of ponies.

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.

An investigation of the equine epidermal growth factor system during hyperinsulinemic laminitis.

Equine laminitis is a disease of the digital epidermal lamellae typified by epidermal cell proliferation and structural collapse. Most commonly the disease is caused by hyperinsulinemia, although the pathogenesis is incompletely understood. Insulin can activate the epidermal growth factor (EGF) system in other species and the present study tested the hypothesis that upregulation of EGF receptor (EGFR) signalling is a key factor in laminitis pathophysiology.

The effect of different grazing conditions on the insulin and incretin response to the oral glucose test in ponies.

Background: The oral glucose test (OGT) is a useful tool for diagnosing insulin dysregulation (ID) and is somewhat repeatable in ponies under consistent management. This study aimed to determine whether the insulin and incretin responses to an OGT in ponies differed after short-term access to fertilised pasture, compared to unfertilised pasture, by using a randomised, repeated measures study design. Sixteen mixed-breed ponies were classified as severely insulin-dysregulated (SD; post-prandial insulin ≥80 μIU/mL) or not severely insulin-dysregulated (NSD; post-prandial insulin < 80 μIU/mL) using an OGT prior to the study.

The cresty neck score is an independent predictor of insulin dysregulation in ponies.

Generalized obesity, regional adiposity, hyperinsulinemia and hypertriglyceridemia are all potential indicators of equine metabolic syndrome (EMS). This study aimed to assess the relationship between morphometric measurements of body condition and metabolic hormone concentrations in ponies, with and without a neck crest or generalised obesity. Twenty-six ponies were assigned a body condition score (BCS) and cresty neck score (CNS).

Incidence and risk factors for recurrence of endocrinopathic laminitis in horses.

Background: Endocrinopathic laminitis is common in horses and ponies, but the recurrence rate of the disease is poorly defined.

Objectives: To determine the incidence of, and risk factors for, the recurrence of endocrinopathic laminitis.

Animals: Privately owned horses and ponies with acute laminitis (n = 317, of which 276 cases with endocrinopathic laminitis were followed up to study completion).

Phenotypic, hormonal, and clinical characteristics of equine endocrinopathic laminitis.

Background: Equine endocrinopathic laminitis is common and can be associated with an underlying endocrinopathy, such as equine metabolic syndrome (EMS), pituitary pars intermedia dysfunction (PPID), pasture consumption, or any combination of these factors.

Objectives: The aim of the study was to improve the risk assessment capabilities of clinicians, and to inform management strategies, for acute endocrinopathic laminitis by prospectively examining the phenotypic, hormonal, and clinical characteristics of the disease in a large cohort.

Animals: Privately owned horses and ponies (n = 301) of any age, sex, or breed diagnosed with laminitis by a veterinarian.

Insulin and incretin responses to grazing in insulin-dysregulated and healthy ponies.

Background: 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.

Objectives: To determine if there is a difference in the insulin and incretin responses to grazing pasture between insulin-dysregulated and healthy ponies.

Sweet taste receptor inhibitors: Potential treatment for equine insulin dysregulation.

Hyperinsulinemia is a major risk factor for equine laminitis, a debilitating and painful foot condition. Sweet taste receptor (T1R2/3) inhibitors have been used to reduce the insulin and glucose responses to oral carbohydrates in other species. However, their effect in horses has not been investigated.

Equine glucagon-like peptide-1 receptor physiology.

Background: Equine metabolic syndrome (EMS) is associated with insulin dysregulation, which often manifests as post-prandial hyperinsulinemia. Circulating concentrations of the incretin hormone, glucagon-like peptide-1 (GLP-1) correlate with an increased insulin response to carbohydrate intake in animals with EMS. However, little is known about the equine GLP-1 receptor (eGLP-1R), or whether GLP-1 concentrations can be manipulated.

Hyperinsulinemia Down-Regulates TLR4 Expression in the Mammalian Heart.

Toll-like receptors (TLR) are key regulators of innate immune and inflammatory responses and their activation is linked to impaired glucose metabolism during metabolic disease. Determination of whether TLR4 signaling can be activated in the heart by insulin may shed light on the pathogenesis of diabetic cardiomyopathy, a process that is often complicated by obesity and insulin resistance. The aim of the current study was to determine if supraphysiological insulin concentrations alter the expression of TLR4, markers of TLR4 signaling and glucose transporters (GLUTs) in the heart.

A potential role for lamellar insulin-like growth factor-1 receptor in the pathogenesis of hyperinsulinaemic laminitis.

The reason why a sustained high concentration of insulin induces laminitis in horses remains unclear. Cell proliferation occurs in the lamellae during insulin-induced laminitis and in other species high concentrations of insulin can activate receptors for the powerful cell mitogen, insulin-like growth factor (IGF)-1. The first aim of this study was to determine if IGF-1 receptors (IGF-1R) are activated in the hoof during insulin-induced laminitis.