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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-IRE1  α  , IRE1  α  , 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.

Exendin-4 Protects MIN6 Cells from t-BHP-Induced Apoptosis via IRE1-JNK-Caspase-3 Signaling