The role of Beclin1 and Atg7 in the protective effect of vildagliptin on islet β cells of db/db mice

Abstract

Objective To investigate the influence of vildagliptin on the expressions of autophagy related genes in islet β cells and β cell survival in diabetic mice.Methods Sixteen db/db mice were allocated into two groups according to the blood glucose levels: diabetic group(DM group,n =8) and vildagliptin treatment group(VTgroup,n=8); the difference of blood glucose levels in DM and VT group was not significant(t=1.918,P ＞0.05).Wildtype mice with the same age were used as normal control group(NC group,n =8).Mice in VT group were administered with vildagliptin (35 mg· kg-1· d-1) by oral garage and mice in DM and NC group were administered with saline.After six weeks of treatment,blood samples collected by cardiac puncture were used to examine plasma HbA1c levels.The morphology of islet was analyzed by immunofluorescence.Apoptosis of islet cells were analyzed by TUNEL method.The mRNA expressions of Beclin1 and Atg7 were determined by RT-PCR.The protein expressions of Beclin1 were examined by immunohistochemistry method.Results Plasma HbA 1c levels in DM group were higher than those in NC group,plasma HbA 1c levels in VT group were lower than that in DM group (F =579.19,P ＜0.01).In contrast to NC group,DM group showed abnormal islet morphology and higher apoptosis rate of β cells (P ＜0.001).In contrast to DM group,VT group showed near normal islet morphology and lower apoptosis rate of β cells(F=37.25,P ＜0.01).RT-PCR analysis demonstrated the expressions of Beclin1 and Atg7 mRNA increased markedly inDMgroupcomparedwithNC group(P＜0.001) and decreased in VT group in comparison with DM group (F =61.35,41.43,all P ＜0.001).Beclin1 protein expressions increased significantly in DM group compared to NC group (P＜0.01)and decreased in VT group,compared to DM group (F =15.92,P ＜0.05).Conclusion Treatment with vildag liptin downregulates expressions of Beclin1 and Atg7 in islet β cells of diabetic mice,which may contribute to improved islet architecture and β cells survival. Key words: Type 2 diabetes mellitus ; Autophagy ; Apoptosis ; Beclin1 ; Atg7 ;