Unacylated as well as acylated ghrelin promotes cell survival and inhibit apoptosis in HIT-T15 pancreatic β -cells

Ghrelin is mainly produced by the stomach, although it is expressed in other tissues, including the pancreas. Among its pleiotropic actions, ghrelin prevents the development of diabetes in rats and exerts mitogenic and antiapoptotic effects in different cell types. In addition, a ghrelin -producing e-cell population has been demonstrated in rodent islets, suggesting a direct role in the control of islet cell survival. In this study, we investigated the effect of acylated ghrelin (AG) and unacylated ghrelin (UAG) on cell survival of HIT-T15 pancreatic β cells. We show that both AG and UAG equally prevented β cell death induced by serum withdrawal. In addition, both peptides inhibited serum starvation-induced apoptosis. These findings indicate that UAG and AG prevent cell death and apoptosis of pancreatic β cells. Since only AG, but not UAG, binds the GRLN receptor, a different and as yet unknown receptor is likely involved in these survival mechanisms.