Products of the Ghrelin Gene, the Pancreatic β-Cell and the Adipocyte

The ghrelin system comprises acylated ghrelin (AG), unacylated ghrelin (UAG) and obestatin, besides the receptor for AG, the growth hormone (GH) secretagogue receptor type 1a (GHS-R1a), and the enzyme-promoting ghrelin acylation, ghrelin O -acyltransferase (GOAT). The ghrelin peptides exert a variety of biological actions, including regulation of energy homeostasis and glucose metabolism, as well as survival and proliferative effects in different cell types. Besides the stomach, its main site of production, ghrelin is expressed in pancreatic islets, where it represents an independent islet cell population. AG exerts insulinostatic actions, UAG has been shown to oppose the AG inhibitory effects on insulin secretion, and obestatin has demonstrated insulinotropic activities. Although differences exist in the regulation of glucose homeostasis, all peptides display survival and antiapoptotic actions in pancreatic β-cells, preserving β-cell mass and function 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. Indeed, AG, UAG and obestatin promote adipogenesis and glucose uptake, and inhibit adipocyte lipolysis. Interestingly, despite similar effects at the cellular level, results from ghrelin, GHS-R and GOAT knockout mice have indicated that AG display diabetogenic effects in vivo. Conversely, UAG and obestatin positively regulate glucose metabolism, and a new role has been recently proposed for obestatin, which was found to improve adipocyte function and insulin sensitivity.