Ghrelin signalling in β-cells regulates insulin secretion and blood glucose

Insulin secretion from pancreatic isletβ-cells is stimulated by glucose. Glucose-induced insulin release is potentiated or suppressed by hormones and neural substances. Ghrelin, an acylated 28-amino acid peptide, was isolated from the stomach in 1999 as the endogenous ligand for the growth hormone (GH) secretagogue-receptor (GHS-R). Circulating ghrelinis produced predominantly in the stomach and to a lesser extent in the intestine, pancreas and brain. Ghrelin, initially identified as a potent stimulator of GH release and feeding, has been shown to suppress glucose-induced insulin release. This insulinostatic action is mediated by Gαi2 subtype of GTP-binding proteins and delayed outward K+ (Kv) channels. Interestingly, ghrelinis produced in pancreatic islets. The ghrelinoriginating from isletsrestricts insulin release and thereby upwardly regulates the systemic glucose level. Furthermore, blockade or elimination of ghrelinenhances insulin release, which can ameliorate glucose intolerance in high-fat diet fed mice and ob/ob mice. This review focuses on the insulinostatic action of ghrelin, its signal transduction mechanisms in isletβ-cells, ghrelin's status as an islethormone, physiological roles of ghrelinin regulating systemic insulin levels and glycaemia, and therapeutic potential of the ghrelin-GHS-R system as the target to treat type 2 diabetes.