Ghrelin Is Present in Pancreatic α-Cells of Humans and Rats and Stimulates Insulin Secretion

TLDR

Ghrelin is a 28‑amino acid peptide that stimulates growth hormone release and regulates feeding, energy metabolism, and gastric acid secretion. The authors localized ghrelin in human and rat pancreas using specific antibodies and immunohistochemistry, and confirmed its presence and mRNA expression in islets by HPLC, radioimmunoassays, and gene detection. Ghrelin is produced by α‑cells in the periphery of islets, elevates β‑cell intracellular Ca²⁺, stimulates insulin secretion, and thus may regulate islet function in an endocrine or paracrine manner.

Abstract

Ghrelin, a novel growth hormone–releasing peptide isolated from human and rat stomach, is a 28–amino acid peptide with a posttranslational acylation modification that is indispensable for stimulating growth hormone secretion by increasing intracellular Ca2+ concentration. It also functions in the regulation of feeding behavior, energy metabolism, and gastric acid secretion and motility. Using two different antibodies against the NH2- and COOH-terminal regions of ghrelin, we studied its localization in human and rat pancreas by immunohistochemistry. Ghrelin-immunoreactive cells were identified at the periphery of pancreatic islets in both species. Ghrelin co-localized exclusively with glucagon in rat islets, indicating that it is produced in α-cells. We identified ghrelin and des-acyl ghrelin in the rat pancreas using reverse-phase high-performance liquid chromatography combined with two radioimmunoassays. We also detected mRNA encoding ghrelin and its receptor in the rat pancreatic islets. Ghrelin increased the cytosolic free Ca2+ concentration in β-cells and stimulated insulin secretion when it was added to isolated rat pancreatic islets. These findings indicate that ghrelin may regulate islet function in an endocrine and/or paracrine manner.