Effects Of Transcription Factor FoxO1 And Resveratrol On Survival Of Pancreatic β-cells And Investigation Of Their Mechanism

Objective (1)To observe the role of transcription factor FoxO1 on the survival of INS-1 cells.(2) To investigate the effect of resveratrol on INS-1 cell proliferation and apoptosis.(3) To explore the mechanism of resveratrol on INS-1 cell survival.Methods.(1)INS-1 cells were cultured in different concentration of glucose and resveratrol,and then the expression of FoxO1 protein was detected by the method of Western blot.(2)The proliferation of INS-1 cells,cultured in insulin and resveratrol,was determined by the method of CCK-8.(3)The proliferation of INS-1 cells which were cultured in different concentration of glucose and resveratrol was determined by the method of CCK-8.(4)The apoptosis of INS-1 cells,cultured in different concentration of resveratrol,was measured by the method of flow cytometry and Tunel.(5)The expression of Bcl-2,Bax,CHOP and IRE1αproteins in INS-1 cells which were cultured in different congcentration of resveratrol was detected by the method of Western blot.Results (1)The expression of FoxO1 was enhanced with the increase of glucose concentration,and resveratrol had no effect on its expression in high glucose level.(2)The proliferation of INS-1 cells had no significant difference between insulin and non-insulin groups.(3)The proliferation of INS-1 cells,cultured in different concentration of glucose for 48 hours, was inhibited in the group with 40μM resveratrol compared with the group without it.(4)In the concentration of 15mM glucose,resveratrol supressed the proliferation and induced the apoptosis of INS-1 cells with the time- and dose-effect relationship.(5)The expression of Bcl-2 was decreased with the increase of resveratrol concentration,meanwhile Bax was enhanced.(6)The expression of CHOP and IRE1αwas enhanced with the increase of resveratrol concentration. Conclusion (1)Glucose was essential to maintain the function of pancreaticβ-cells, and with the concentration-dependent manner, promoted its proliferation in a certain degree. The high glucose level for a certain time may enhance the expression of FoxO1.(2)Resveratrol affected the survival of pancreaticβ-cells through the signaling pathways without FoxO1.(3)Resveratrol inhibited the proliferation and induced apoptosis of pancreaticβ-cells in concentration- and time-dependent ways.(4) Resveratrol induced the apoptosic of pancreaticβ-cells through endocytoplasmic reticulum stress which was regulated by Bcl-2 and Bax.