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

Nicolas C Galinelli; Nicholas J Bamford; Madison L Erdody; Tobias Warnken; Melody A de Laat; Martin N Sillence; Patricia A Harris; Simon R Bailey

doi:10.1016/j.domaniend.2024.106893

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

Domest Anim Endocrinol. 2024 Oct 20:90:106893. doi: 10.1016/j.domaniend.2024.106893. Online ahead of print.

Authors

Nicolas C Galinelli¹, Nicholas J Bamford¹, Madison L Erdody¹, Tobias Warnken², Melody A de Laat³, Martin N Sillence³, Patricia A Harris⁴, Simon R Bailey⁵

Affiliations

¹ Melbourne Veterinary School, The University of Melbourne, Parkville, Victoria, Australia.
² Boehringer Ingelheim Vetmedica GmbH, Ingelheim am Rhein, Germany.
³ School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia.
⁴ Equine Studies Group, Waltham Petcare Science Institute, Melton Mowbray, United Kingdom.
⁵ Melbourne Veterinary School, The University of Melbourne, Parkville, Victoria, Australia. Electronic address: bais@unimelb.edu.au.

PMID: 39486097
DOI: 10.1016/j.domaniend.2024.106893

Abstract

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. The aim of this study was to investigate the effects of alpha-methyl-para-tyrosine (AMPT), a tyrosine hydroxylase inhibitor that reduces dopamine production, on insulin sensitivity and the post-prandial insulin response to a glucose-containing meal. Six healthy Standardbred horses were enrolled in a placebo-controlled randomised crossover study, in which one dose of AMPT (40 mg/kg BW) or placebo was administered orally, prior to performing an in-feed oral glucose test (OGT) and a frequently sampled intravenous glucose tolerance test (FSIGTT). Dopamine reduction by AMPT was confirmed by an increase in plasma prolactin concentration and the lack of post-prandial increase in plasma dopamine concentration compared to placebo. Post-prandial insulin responses, both peak and AUCi, were increased after AMPT compared to placebo (P=0.048 and P=0.005, respectively), without affecting blood glucose concentrations. However, one dose of AMPT did not appear to affect tissue sensitivity as assessed by the FSIGTT. This study confirmed that dopamine plays a role in the regulation of insulin secretion in horses, as it does in other species, whereby the post-prandial release of dopamine into the circulation may inhibit pancreatic insulin secretion. Further studies are required to evaluate different dosing protocols for AMPT, and to further investigate the links between PPID, ID and laminitis risk in horses.

Keywords: Adrenocorticotropic hormone; Equine; Insulin dysregulation; Pituitary pars intermedia dysfunction; Prolactin.