Equine glucagon-like peptide-1 receptor physiology

Murad H Kheder; Simon R Bailey; Kevin J Dudley; Martin N Sillence; Melody A de Laat

doi:10.7717/peerj.4316

Equine glucagon-like peptide-1 receptor physiology

PeerJ. 2018 Jan 29:6:e4316. doi: 10.7717/peerj.4316. eCollection 2018.

Authors

Murad H Kheder¹, Simon R Bailey², Kevin J Dudley³, Martin N Sillence¹, Melody A de Laat¹

Affiliations

¹ Science and Engineering Faculty, Queensland University of Technology, Brisbane, Queensland, Australia.
² Faculty of Veterinary and Agricultural Sciences, University of Melbourne, Melbourne, Victoria, Australia.
³ Institute for Future Environments, Queensland University of Technology, Brisbane, Queensland, Australia.

Abstract

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. The objectives were to determine (1) the tissue localisation of the eGLP-1R, (2) the GLP-1 secretory capacity of equine intestine in response to glucose and (3) whether GLP-1 stimulated insulin secretion from isolated pancreatic islets can be attenuated.

Methods: Archived and abattoir-sourced tissues from healthy horses were used. Reverse transcriptase PCR was used to determine the tissue distribution of the eGLP-1R gene, with immunohistochemical confirmation of its pancreatic location. The GLP-1 secretion from intestinal explants in response to 4 and 12 mM glucose was quantified in vitro. Pancreatic islets were freshly isolated to assess the insulin secretory response to GLP-1 agonism and antagonism in vitro, using concentration-response experiments.

Results: The eGLP-1R gene is widely distributed in horses (pancreas, heart, liver, kidney, duodenum, digital lamellae, tongue and gluteal skeletal muscle). Within the pancreas the eGLP-1R was immunolocalised to the pancreatic islets. Insulin secretion from pancreatic islets was concentration-dependent with human GLP-1, but not the synthetic analogue exendin-4. The GLP-1R antagonist exendin 9-39 (1 nM) reduced (P = 0.08) insulin secretion by 27%.

Discussion: The distribution of the eGLP-1R across a range of tissues indicates that it may have functions beyond insulin release. The ability to reduce insulin secretion, and therefore hyperinsulinemia, through eGLP-1R antagonism is a promising and novel approach to managing equine insulin dysregulation.

Keywords: Equine metabolic syndrome; GLP-1 receptor; Horse; Incretin; Insulin; Laminitis.

Grants and funding

The study was funded by the Australian Research Council who had no role in the conception or execution of the study. All reagents were purchased at full cost for the purpose of the study. Dr. de Laat was supported by an Australian Research Council Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.