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Peptides. 2018 Feb;100:236-242. doi: 10.1016/j.peptides.2017.12.015.

Ghrelin regulation of glucose metabolism.

Author information

1
Institute for Diabetes and Obesity, Helmholtz Diabetes Center (HDC), Helmholtz Zentrum München and German National Diabetes Center (DZD), 85764, Neuherberg, Germany.
2
Institute for Diabetes and Obesity, Helmholtz Diabetes Center (HDC), Helmholtz Zentrum München and German National Diabetes Center (DZD), 85764, Neuherberg, Germany; Division of Metabolic Diseases, Department of Medicine, Technische Universität München, 80333, Munich, Germany.
3
Institute for Diabetes and Obesity, Helmholtz Diabetes Center (HDC), Helmholtz Zentrum München and German National Diabetes Center (DZD), 85764, Neuherberg, Germany. Electronic address: timo.mueller@helmholtz-muenchen.de.

Abstract

The a 28-amino acid peptide ghrelin was discovered in 1999 as a growth hormone (GH) releasing peptide. Soon after its discovery, ghrelin was found to increase body weight and adiposity by acting on the hypothalamic melanocortinergic system. Subsequently, ghrelin was found to exert a series of metabolic effects, overall testifying ghrelin a pleiotropic nature of broad pharmacological interest. Ghrelin acts through the growth hormone secretagogue-receptor (GHS-R), a seven transmembrane G protein-coupled receptor with high expression in the anterior pituitary, pancreatic islets, thyroid gland, heart and various regions of the brain. Among ghrelins numerous metabolic effects are the most prominent the stimulation of appetite via activation of orexigenic hypothalamic neurocircuits and the food-intake independent stimulation of lipogenesis, which both together lead to an increase in body weight and adiposity. Ghrelin effects beyond the regulation of appetite and GH secretion include the regulation of gut motility, sleep-wake rhythm, taste sensation, reward seeking behaviour, and the regulation of glucose metabolism. The latter received recently increasing recognition because pharmacological inhibition of ghrelin signaling might be of therapeutic value to improve insuin resistance and type 2 diabetes. In this review we highlight the multifaceted nature of ghrelin and summarize its glucoregulatory action and discuss the pharmacological value of ghrelin pathway inhibition for the treatment of glucose intolerance and type 2 diabetes.

KEYWORDS:

Diabetes; Diet-induced obesity; Ghrelin; Glucose metabolism; Insulin sensitivity

PMID:
29412824
PMCID:
PMC5805851
DOI:
10.1016/j.peptides.2017.12.015
[Indexed for MEDLINE]
Free PMC Article

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