Ghrelin inhibit cell apoptosis in pancreatic beta cell line HIT-T15 via mitogen-activated protein kinase/phosphoinositide 3-kinase pathways.
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.
Zhang
Yuwei
Y
Department of Endocrinology, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou, Sichuan, PR China.
Ying
Binwu
B
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Shi
LiXin
L
Department of Endocrinology, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou, Sichuan, PR China.
Fan
Hong
H
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China; Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Yang
Dongmei
D
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Xu
Dan
D
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Wei
Yonggang
Y
Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Hu
Xiaobo
X
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Zhang
Yonggang
Y
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Zhang
Xiaohong
X
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Wang
Tao
T
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Liu
Daishun
D
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Dou
Liyang
L
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Chen
Guo
G
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Jiang
Fei
F
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
Wen
Fuqiang
F
Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China. Electronic address: wenfuqiang@126.com.
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D006224:Cricetinae; D004317:Doxorubicin / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D054439:Ghrelin; D020287:In Situ Nick-End Labeling; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000201:enzymology; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D036361:Peptide Hormones / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D013997:Time Factors
D004317:Doxorubicin; D004791:Enzyme Inhibitors; D054439:Ghrelin; D020928:Mitogen-Activated Protein Kinases; D036361:Peptide Hormones; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors