The Effect Of Exenatide On Autophagy In Human Embryonic Kidney Cells 293(KEK293 Cells) Under High-glucose Conditions

Aim:The aim of this study was to investigate the effects of exenatide on autophagy in human embryonic kidney cells 293(HEK293 cells)under high-glucose conditions.Methods: MTT assay was used to determine the effect of different concentrations of glucose(50,100 mM)on the survival rate of HEK293 cells at different time(24,48,72h),and the cell viability of the high glucose treated HEK293 cells in response toexenatide.After HEK293 cells was treated by high glucose and exenatide 48 h,western blotting was used to analyze the expression levels of LC3 II and Bcl-2.Effect of autophagy inhibitor 3-MA on protective effect of exenatide on cells treated by high glucose was determined by MTT Assay.The HEK/GLP1R/CRE/Luc cell model was established.The luciferase reporter assay was used to compare the potency of exenatide to glucagon-like peptide-1(GLP-1),determine the stimulating response ofexenatide to cells at different concentrations of glucose and determine the stimulating response of exenatide to cells under the autophagy inhibitor 3-MA.Results: Under high-glucose conditions,the cell growth was both supressed in a concentration-dependent and time-dependent manner,and exenatide improved the viability of high-glucose treated cells.The expression level of LC3-II showed that exenatide induced autophagy and inhibited apoptosis in high glucose condition.The protection of exenatide to cells treated by high-glucose was blocked by co-treatment with 3-MA.The results of luciferase reporter assay showed that the potency of exenatide and glucagon-like peptide-1(GLP-1)was similar,and the stimulating response of exenatide to cells was relative to concentrations of glucose and stimulating time.The stimulating response of exenatide to cells was lower when the autophagy was supressed.Conclusion: High concentration of glucose inhibits the growth of HEK293 cells,exenatide dose-dependent improve the autophagy function of HEK293 cells and reduce the cell apoptosis under high concentration of glucose.Thereforeexenatideprotected HEK293 cells from the damage of high-glucose by the induction of autophagy.