Liver‐Expressed Antimicrobial Peptide 2 antagonizes the insulinostatic effect of ghrelin in rat isolated pancreatic islets

• Published in: Fundamental & clinical pharmacology 2022-04, Vol.36 (2), p.375-377
• Main Authors: Bayle, Morgane, Péraldi‐Roux, Sylvie, Gautheron, Guillaume, Cros, Gérard, Oiry, Catherine, Neasta, Jérémie
• Format: Article
• Language: English
• Subjects: Animals; Antiinfectives and antibacterials; Antimicrobial Cationic Peptides - metabolism; Antimicrobial Cationic Peptides - pharmacology; Antimicrobial peptides; Endocrinology and metabolism; G protein-coupled receptors; Ghrelin; Ghrelin - metabolism; Ghrelin - pharmacology; GHS‐R1a; Glucose; Growth hormones; Human health and pathology; Hépatology and Gastroenterology; Insulin; Insulin - metabolism; Insulin secretion; islets; Islets of Langerhans; Islets of Langerhans - drug effects; Islets of Langerhans - metabolism; LEAP2; Life Sciences; Liver; Pancreas; Peptides; Pharmaceutical sciences; Pharmacology; Rats; Receptors; Receptors, Ghrelin - metabolism; Secretion
• ISSN: 0767-3981; 1472-8206
• DOI: 10.1111/fcp.12722

The hormone ghrelin is the endogenous agonist of the G protein‐coupled receptor (GPCR) termed growth hormone secretagogue receptor (GHSR). Ghrelin inhibits glucose‐stimulated insulin secretion by activating pancreatic GHSR. Recently, Liver‐Expressed Antimicrobial Peptide 2 (LEAP2) was recognized as an endogenous GHSR ligand that blocks ghrelin‐induced actions. Nonetheless, the effect of LEAP2 on glucose‐stimulated insulin secretion from pancreatic islets is unknown. We aimed at exploring the activity of LEAP2 on glucose‐stimulated insulin secretion. Islets of Langerhans isolated from rat pancreas were exposed to glucose in the presence or in the absence of LEAP2 and ghrelin and then insulin secretion was assayed. LEAP2 did not modulate glucose‐stimulated insulin secretion. However, LEAP2 blocked the insulinostatic action of ghrelin. Our data show that LEAP2 behaves as an antagonist of pancreatic GHSR.