Effect And Possible Mechanism Of Angiotensin(1-7) On Autophagy In MIN6 Pancreatic Beta Cells

Objective:This study was aim to investigate the role of angiotensin(1-7)and its possible mechanism on autophagy in the mouse pancreatic beta cell line MIN6 cells incubated with glucolipotoxicity.Methods:MIN6 beta cells were cultured in high glucose DMEM medium supplemented with 15% fetal bovine serum(FBS)and 1%streptomycin-penicillin solution at 37? in a humidified atmosphere containing 5% CO2 prior to treatment.Cells were divided into the following four groups: the control group(CON),the high glucose and high fat group(HGHF),the Ang(1-7)incubation group,and the A779 treatment group.Cells were incubated for 12 hours after treatment respectively.DAPI staining was applied to observe the apoptotic cells by fluorescent microscopy.The apoptotic cells were determinated by the Cell Counting Kit-8(CCK-8).The expressions of autophagyic proteins Beclin 1,p62 and the phosphorylation of Akt(p-Akt)was detected by Western blotting.Results:Compared with the control group,glucolipotoxicity significantly enhanced cell apoptosis(P < 0.05)and the expression of autophagic protein p62 and Beclin1(both of P < 0.05),strongly decreased the cell viability(P < 0.05)and the expresson of phosphorylation of Akt and mTOR(both of P<0.05).Compared with the HGHF group,angiotensin(1-7)reduced apoptosis rate(P<0.05)and the level of p62 and Beclin1(both of P<0.05)in the presence of glucolipotoxicity,promoted cell survival(P<0.05)and the phosphorylation of Akt and mTOR(both of P<0.05).Compared with the angiotensin(1-7)treatment group,A779 pretreatment group increased apoptosis(P<0.05)and the expression of p62 and Beclin 1(both of P<0.05)incubated with angiotensin(1-7)in combination with glucolipotoxicity,attenuated cell survival(P<0.05)andthe phosphorylation of Akt and mTOR(both of P<0.05).Conclusion:It is suggested for the first time that Ang(1-7)could largely depress ?-cell autophagy induced by glucolipotoxicity,decrease the apoptosis of ?-cell,and promote ?-cell survival,which may be achieved by activating the Akt/mTOR signaling pathway.