title: Ghrelin inhibit cell apoptosis in pancreatic beta cell line HIT-T15 via mitogen-activated protein kinase/phosphoinositide 3-kinase pathways.
abstract: 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.
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou, Sichuan, PR China.
authors.forename: Yuwei
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: 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.
authors.forename: Binwu
authors.initials: B
authors.lastname: Ying
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Guiyang Medical College, Guiyang 550004, Guizhou, Sichuan, PR China.
authors.forename: LiXin
authors.initials: L
authors.lastname: Shi
authors.affiliation: 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.
authors.forename: Hong
authors.initials: H
authors.lastname: Fan
authors.affiliation: Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Yang
authors.affiliation: Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors.forename: Dan
authors.initials: D
authors.lastname: Xu
authors.affiliation: Department of General Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Hu
authors.affiliation: Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors.forename: Xiaohong
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.affiliation: Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors.forename: Daishun
authors.initials: D
authors.lastname: Liu
authors.affiliation: Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors.forename: Liyang
authors.initials: L
authors.lastname: Dou
authors.affiliation: Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.affiliation: Division of Pulmonary Disease, State Key Laboratory of Biotherapy and Department of Respiratory Medicine, West China Hospital, Sichuan University, Chengdu 610041, Sichuan, PR China.
authors.forename: Fei
authors.initials: F
authors.lastname: Jiang
authors.affiliation: 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.
authors.forename: Fuqiang
authors.initials: F
authors.lastname: Wen
mesh_terms: 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
chemical_list: D004317:Doxorubicin; D004791:Enzyme Inhibitors; D054439:Ghrelin; D020928:Mitogen-Activated Protein Kinases; D036361:Peptide Hormones; D019869:Phosphatidylinositol 3-Kinases; D000081082:Phosphoinositide-3 Kinase Inhibitors