title: Exendin-4 Protects MIN6 Cells from t-BHP-Induced Apoptosis via IRE1-JNK-Caspase-3 Signaling.
abstract: Objectives. This study aimed to explore the effect of exendin-4 on t-BHP-induced apoptosis in pancreatic β cells and the mechanism of action. Methods. Murine MIN6 pancreatic β cells were treated with exendin-4 in the presence or absence of tert-butyl hydroperoxide (t-BHP). Cell survival was assessed by MTT staining. The percentage of apoptotic cells was determined by fluorescence microscopy analysis after Hoechst/PI staining and flow cytometric assay after Annexin V-FITC/PI staining. The activity of caspase-3 was determined using a caspase-3 activity kit. Expression of P-IRE1α, IRE1α, C-Jun N-terminal kinase (JNK), P-JNK, C-JUN, and P-C-JUN was detected by western blotting. Results. Exendin-4 was found to inhibit t-BHP-induced apoptosis in pancreatic β-cells by downregulating caspase-3 activity. Exendin-4 also inhibited the endoplasmic reticulum transmembrane protein IRE1, the apoptosis-related signaling molecule JNK, and c-Jun activation. Conclusions. Our findings suggest that exendin-4 ultimately reduces t-BHP-induced β-cell apoptosis. IRE1-JNK-c-Jun signaling is involved in the exendin-4-mediated modulation of β-cell apoptosis.
authors.affiliation: Department of Endocrinology, Fujian Institute of Endocrinology, Union Hospital of Fujian Medical University, Fuzhou, Fujian 350001, China.
authors.forename: Wen-Jia
authors.initials: WJ
authors.lastname: Chen
authors.forename: Lin-Xi
authors.initials: LX
authors.lastname: Wang
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Zhou
authors.initials: Z
authors.lastname: Chen
authors.forename: Xiao-Ying
authors.initials: XY
authors.lastname: Liu
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Liu
authors.forename: Li-Bin
authors.initials: LB
authors.lastname: Liu