Effective strategy to treat type 2 diabetes by blockade of ghrelin signaling in islet β-cells

点击翻译按钮获取中文摘要

Ghrelin, an acylated 28-amino acid peptide, was isolated from the stomach as the endogenous ligand for growth hormone-secretagogue receptor (GHS-R). In addition to its unique role in regulating mealtime hunger and lipid metabolism, we have reported the physiological role of ghrelin in the regulation of insulin release and glucose metabolism. In this study, we uncovered that the signal transduction mechanisms of ghrelin in islet β-cells are very unique, being distinct from those utilized for growth hormone release. In type 2 diabetec GK rats, blockade of β-cell ghrelin receptor enhanced insulin release and prevents impaired glucose tolerance. Thus, manipulation of insulinostatic function of ghrelin?GHS-R system in islets could optimize the amount of insulin release to meet the systemic demand, providing a potential therapeutic application to prevent type 2 diabetes.