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

Abstract EN

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.