Abstract: Abstract: Objective　To explore the protective effect of Exendin-4 on human islet amyloid polypeptide (hIAPP)-induced pancreatic β-cell apoptosis and its possible mechanism. Methods　INS-1E cells were cultured with 2.5, 5, 10, 20 μmol/L hIAPP to establish apoptosis model. Exendin-4 20, 50 and 100 nmol/L pretreated for 24 h followed by hIAPP treatment for 48 h. CCK-8 assay was used to detect cell viability and to screen effective dosage. Experiments were divided into the control group, the Exendin-4 group, the hIAPP group and the hIAPP+Exendin-4 group. The change of membrane permeability was detected by LDH release detection kit and the generation of intracellular ATP was detected by chemiluminescence assay. JC-1 fluorescence probe was used to detect the change of mitochondrial membrane potential. Western blot assay was used to detect the expression of mitochondrial apoptosis-related proteins Bcl-2, Bax and Bad. Results　Compared to the control group, hIAPP (20 μmol/L) can significantly inhibit cell proliferation, increase LDH release and intracellular ATP consumption, increase the ratio of depolarized mitochondrial membrane potential, down-regulate Bcl-2 expression, and up-regulate Bax and Bad protein (P＜0.05). However, hIAPP+Exendin-4 group can significantly improve cell viability, reduce LDH release, increase ATP production, reduce the proportion of depolarized mitochondrial membrane potential, up-regulate Bcl-2 and down-regulate the expression of Bax and Bad protein (P＜0.05). Exendin-4 alone had no effect on cell growth. Conclusion　Exendin-4 has a protective effect on hIAPP-induced apoptosis of pancreatic β-cells, which is related to the inhibition of mitochondrial apoptosis pathway.

Key words:  islet amyloid polypeptide, insulin-secreting cells, apoptosis, Exendin-4, pancreatic β-cells, mitochondrial apoptosis