Gastrointestinal hormones: Edited by Christian WeberThe ghrelin O-acyltransferase–ghrelin system: a novel regulator of glucose metabolismHeppner, Kristy Ma; Tong, Jennya; Kirchner, Henriettea; Nass, Ralfb; Tschöp, Matthias HaAuthor Information aDepartment of Medicine, Metabolic Diseases Institute, University of Cincinnati, Cincinnati, Ohio, USA bDepartment of Medicine, University of Virginia, Charlottesville, Virginia, USA Correspondence to Matthias H. Tschöp, MD, Metabolic Diseases Institute, University of Cincinnati, 2170 East Galbraith Road A-123, Cincinnati, OH 45237, USA Tel: +1 513 558 8648; e-mail: [email protected] Current Opinion in Endocrinology, Diabetes and Obesity: February 2011 - Volume 18 - Issue 1 - p 50-55 doi: 10.1097/MED.0b013e328341e1d3 Buy Metrics Abstract Purpose of review Ghrelin, an orexigenic hormone secreted from the stomach, exists in the circulation in two isoforms: des-acyl and acyl ghrelin. Acylation by the enzyme ghrelin O-acyl-transferase (GOAT) enables ghrelin to activate the ghrelin receptor. This review discusses recent findings illustrating the role of acyl ghrelin, des-acyl ghrelin and GOAT in regulating glucose homeostasis. Recent findings Recent publications support a role of ghrelin in modulating glucose homeostasis. Novel cellular mechanisms have been proposed to explain these effects. Controversy on this topic continues to exist owing to inconsistent observations made in both rodents and humans. Many recent studies are uncovering a role of des-acyl ghrelin in glucose metabolism specifically in modulating insulin sensitivity and glucose uptake into adipocytes. A novel role of ghrelin acylation by the enzyme GOAT in regulating glucose metabolism during caloric deprivation has newly been discovered. Summary Ghrelin plays a role in regulating glucose homeostasis through the modulation of insulin secretion and insulin sensitivity. Acyl ghrelin and des-acyl ghrelin appear to have opposing glucoregulatory effects and regulation of acylation by the enzyme GOAT appears to play a role in mediating glucose metabolism. Modulation of GOAT or ghrelin signaling may be a clinically relevant strategy to treat metabolic diseases such as type II diabetes. Copyright © 2011 Wolters Kluwer Health, Inc. All rights reserved.