Mechanisms in endocrinology: regulation of glucose metabolism by the ghrelin system: multiple players and multiple actions.
Ghrelin is a 28-amino acid peptide secreted mainly from the X/A-like cells of the stomach. Ghrelin is found in circulation in both des-acyl (dAG) and acyl forms (AG). Acylation is catalyzed by the enzyme ghrelin O-acyltransferase (GOAT). AG acts on the GH secretagogue receptor (GHSR) in the CNS to promote feeding and adiposity and also acts on GHSR in the pancreas to inhibit glucose-stimulated insulin secretion. These well-described actions of AG have made it a popular target for obesity and type 2 diabetes mellitus pharmacotherapies. However, despite the lack of a cognate receptor, dAG appears to have gluco-regulatory action, which adds an additional layer of complexity to ghrelin's regulation of glucose metabolism. This review discusses the current literature on the gluco-regulatory action of the ghrelin system (dAG, AG, GHSR, and GOAT) with specific emphasis aimed toward distinguishing AG vs dAG action.
Division of DiabetesObesity and Metabolism, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA andDivision of EndocrinologyDiabetes and Metabolism, Department of Medicine, University of Cincinnati, 260 Stetson Street, Suite 4200, Cincinnati, Ohio 45219-0547, USA.
Kristy M
KM
Heppner
Division of DiabetesObesity and Metabolism, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, Oregon, USA andDivision of EndocrinologyDiabetes and Metabolism, Department of Medicine, University of Cincinnati, 260 Stetson Street, Suite 4200, Cincinnati, Ohio 45219-0547, USA jenny.tong@uc.edu.
Jenny
J
Tong
D000215:Acylation; D000818:Animals; D004704:Endocrinology; D054439:Ghrelin / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism; D006801:Humans; D054440:Receptors, Ghrelin / Q000378:metabolism*
D054439:Ghrelin; D054440:Receptors, Ghrelin; D005947:Glucose