ISSN 1470-3947 (print)
ISSN 1479-6848 (online)

Searchable abstracts of presentations at key conferences in endocrinology

Published by BioScientifica
Endocrine Abstracts (2010) 22 S2.3 
|

Unacylated ghrelin: a metabolic hormone

Riccarda Granata

Author affiliations

Ghrelin was identified in the stomach as the endogenous ligand of the GH secretagogue receptor type 1a (GHS-R1a). Acylated ghrelin (AG), through interaction with GHS-R1a, exerts many central and peripheral effects, including stimulation of GH secretion and food intake. Unacylated ghrelin (UAG), although unable to bind the GHS-R1a and devoid of endocrine actions is an active peptide, exerting pleiotropic effects through an unknown receptor. UAG has been shown to act as an antagonist of AG in glycemic control. Indeed, AG induces hyperglycemia and reduces insulin secretion in humans, whereas UAG antagonizes these effects. Moreover, AG-induced decrease in insulin sensitivity is counteracted by coinjection of UAG in GH deficient patients. Furthermore, AG stimulates whereas UAG inhibits glucose output by primary hepatocytes Transgenic mice overexpressing UAG in pancreatic islets show increased insulin sensitivity, and UAG overexpression in adipose tissue results in improved glucose tolerance and insulin sensitivity. UAG even inhibits isoproterenol-induced lipolysis in rat adipocytes. These findings suggest positive effects of UAG on glucose metabolism, likely through a receptor(s) different from the GHS-R1a. In the endocrine pancreas, UAG protects β-cells and human islets against cytokine-and glucolipotoxicity-induced apoptosis, stimulates β-cell proliferation and enhances glucose-induced insulin secretion. Interestingly, small UAG fragments also display insulinotropic, survival and antiapoptotic effects in β-cells and human islets, suggesting that UAG biological activity is not strictly dependent on length of the peptide. UAG increases glucose uptake in β-cells and human islets, further indicating a role in glucose homeostasis. In streptozotocin-treated newborn rats, UAG prevents diabetes by improving glucose metabolism and preserving islet cell mass. Importantly, UAG has been also shown to exert cardioprotective effects, both in vitro and in vivo. Therefore, UAG and its analogs may be considered as promising lead compounds for the development of novel therapeutic strategies in the cure of metabolic syndrome and diabetes.

This Issue/Conference

Article tools

My recently viewed abstracts

My recent searches

Search Endocrine Abstracts for...

Search Google Scholar for...

Search PubMed for...