Equine glucagon-like peptide-1 receptor physiology

Area of Science:

• Veterinary Endocrinology
• Equine Physiology
• Molecular Endocrinology

Background:

• Equine metabolic syndrome (EMS) is characterized by insulin dysregulation and hyperinsulinemia.
• Glucagon-like peptide-1 (GLP-1) hormone levels correlate with insulin response in EMS horses.
• The equine GLP-1 receptor (eGLP-1R) and its modulatory potential remain largely uncharacterized.

Purpose of the Study:

• To determine the tissue distribution of the eGLP-1R in horses.
• To assess the GLP-1 secretory capacity of equine intestinal tissue in response to glucose.
• To investigate the potential for attenuating GLP-1-stimulated insulin secretion from isolated pancreatic islets.

Main Methods:

• Reverse transcriptase PCR and immunohistochemistry were used to identify eGLP-1R gene and protein localization.
• Equine intestinal explants were used to quantify GLP-1 secretion in response to varying glucose concentrations in vitro.
• Isolated pancreatic islets were utilized to assess insulin secretion in response to GLP-1 receptor agonism and antagonism in vitro.

Main Results:

• The eGLP-1R gene was detected in multiple equine tissues, including the pancreas, heart, liver, kidney, duodenum, digital lamellae, tongue, and skeletal muscle.
• Immunohistochemistry confirmed eGLP-1R localization within the pancreatic islets.
• Human GLP-1 stimulated insulin secretion from pancreatic islets in a concentration-dependent manner, while the synthetic analogue exendin-4 did not.
• A GLP-1R antagonist, exendin 9-39, significantly reduced insulin secretion by 27% (P = 0.08).

Conclusions:

• The widespread distribution of eGLP-1R suggests diverse physiological roles beyond insulin regulation.
• Targeting the eGLP-1R through antagonism presents a promising therapeutic strategy for managing hyperinsulinemia in horses.
• This research opens novel avenues for understanding and treating equine insulin dysregulation.