Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2014) 35 S20.2 | DOI: 10.1530/endoabs.35.S20.2

ECE2014 Symposia New hormones and endocrine tissues (3 abstracts)

Products of the ghrelin gene, their role in regulating β cell and adipocyte function

Riccarda Granata


Division of Endocrinology, Diabetes and Metabolism, Department of Medical Sciences, University of Torino, Torino, Italy.


The ghrelin system comprises ghrelin, des-acyl ghrelin and obestatin, besides ghrelin receptor, GH secretagogue receptor type 1a (GHS-R1a), and the enzyme promoting ghrelin acylation, ghrelin-O acyl transferase (GOAT). The ghrelin peptides display different biological actions, including regulation of energy homeostasis and glucose metabolism, as well as survival and proliferative effects in different cell types. Besides the stomach, where they are mostly produced, ghrelin, des-acyl ghrelin and obestatin are expressed in the endocrine pancreas, suggesting a role in pancreas development and glucose metabolism. Indeed, ghrelin inhibits insulin secretion and insulin sensitivity, whereas des-acyl ghrelin. counteracts ghrelin inhibitory effects on insulin secretion and improves glucose metabolism. Obestatin, exerts insulinotropic effects, as well as positive actions on glucose homeostasis, likely through binding to the glucagon-like peptide 1 (GLP-1) receptor. Moreover, obestatin was recently found to promote in vitro β-cell generation from mouse pancreatic islet-derived precursors, indicating a major role in β-cell development. Interestingly, all the ghrelin peptides have been shown to display survival and antiapoptotic actions in pancreatic β-cells, both in vitro and in vivo. The ghrelin system is also expressed in adipose tissue, and ghrelin effects have been demonstrated in both white and brown adipocytes. As for pancreatic β-cells, all the peptides exert antiapoptotic actions in white adipocytes and, whereas ghrelin is mostly diabetogenic, both des-acyl ghrelin and obestatin inhibit lipolysis and improve adipocyte function. Of note, obestatin exerts relevant effects on white adipocyte function, by positively regulating glucose homeostasis, likely through interaction with GLP-1R. Obestatin also reduces insulin resistance and prevents inflammation in vivo, by inhibiting pro-inflammatory cytokine release in fat, muscle and liver. Therefore, des-acyl ghrelin and obestatin may be good candidates for regenerative medicine in diabetes and may be used, in association with other compounds, for the treatment of metabolic and inflammatory disorders.

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