Ghrelin inhibit cell apoptosis in pancreatic β cell line HIT-T15 via mitogen-activated protein kinase/phosphoinositide 3-kinase pathways

• DOI: 10.1016/j.tox.2007.05.013
• Publication Date: 2007-05-25T08:49:58Z
• Authors: Yuwei Zhang; Binwu Ying; LiXin Shi; Hong Fan; Dongmei Yang; Dan Xu; Yonggang Wei; Xiaobo Hu; Yonggang Zhang; Xiaohong Zhang; Tao Wang; Daishun Liu; Liyang Dou; Guo Chen; Fei Jiang; Fuqiang Wen
• Keywords: 0301 basic medicine; Time Factors; Cell Survival; Peptide Hormones; Apoptosis; Ghrelin; Cell Line; Phosphatidylinositol 3-Kinases; 03 medical and health sciences; Doxorubicin; Cricetinae; Insulin-Secreting Cells; In Situ Nick-End Labeling; Animals; Enzyme Inhibitors; Mitogen-Activated Protein Kinases; Phosphorylation; Phosphoinositide-3 Kinase Inhibitors

Ghrelin stimulates growth hormone (GH) release and induces positive energy balances. Previous studies have reported that ghrelin inhibits apoptosis in several cell types but the precise underlying protective mechanisms in pancreatic beta cells are poorly understood. Therefore, we investigated which pathway was related with its anti-apoptotic effect in pancreatic beta cells. Exposure of HIT-T15 cells to ghrelin caused a rapid activation of MAPKs and Akt. Chemical inhibitors of MAPK and PI3K blocked the anti-apoptotic of ghrelin. Ghrelin also stimulated the mitochondrial pathways of apoptosis and it showed increased Bcl-2, decreased Bax, prevention cytochrome c release and inhibition of caspase-3 activation in pancreatic beta cell line HIT-T15. Our findings suggest that ghrelin may act as a survival factor that inhibits the apoptotics pathways, and the MAPKs, AKT pathways could be key roles in the apoptosis of pancreatic beta cells.