Editorial
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World J Gastroenterol. Jul 7, 2012; 18(25): 3183-3195
Published online Jul 7, 2012. doi: 10.3748/wjg.v18.i25.3183
Ghrelin's second life: From appetite stimulator to glucose regulator
Pieter-Jan Verhulst, Inge Depoortere
Pieter-Jan Verhulst, Inge Depoortere, Translational Research Center for Gastrointestinal Disorders, Catholic University of Leuven, 3000 Leuven, Belgium
Author contributions: Verhulst PJ reviewed the literature and wrote the manuscript; Depoortere I revised the manuscript critically.
Correspondence to: Inge Depoortere, PhD, Professor, Translational Research Center for Gastrointestinal Disorders, Catholic University of Leuven, KU Leuven, Targid, Gasthuisberg O&N1, PO Box 701, 3000 Leuven, Belgium. inge.depoortere@med.kuleuven.be
Telephone: +32-16-330675 Fax: +32-16-330723
Received: July 1, 2011
Revised: December 1, 2011
Accepted: January 18, 2012
Published online: July 7, 2012
Abstract

Ghrelin, a 28 amino acid peptide hormone produced by the stomach, was the first orexigenic hormone to be discovered from the periphery. The octanoyl modification at Ser3, mediated by ghrelin O-acyltransferase (GOAT), is essential for ghrelin’s biological activity. Ghrelin stimulates food intake through binding to its receptor (GRLN-R) on neurons in the arcuate nucleus of the hypothalamus. Ghrelin is widely expressed throughout the body; accordingly, it is implicated in several other physiological functions, which include growth hormone release, gastric emptying, and body weight regulation. Ghrelin and GRLN-R expression are also found in the pancreas, suggesting a local physiological role. Accordingly, several recent studies now point towards an important role for ghrelin and its receptor in the regulation of blood glucose homeostasis, which is the main focus of this review. Several mechanisms of this regulation by ghrelin have been proposed, and one possibility is through the regulation of insulin secretion. Despite some controversy, most studies suggest that ghrelin exerts an inhibitory effect on insulin secretion, resulting in increased circulating glucose levels. Ghrelin may thus be a diabetogenic factor. Obesity-related type 2 diabetes has become an increasingly important health problem, almost reaching epidemic proportions in the world; therefore, antagonists of the ghrelin-GOAT signaling pathway, which will tackle both energy- and glucose homeostasis, may be considered as promising new therapies for this disease.

Keywords: Ghrelin; Blood glucose; Pancreas; Diabetes; Insulin