Effect of sitagliptin on expression of autophagy related genes in islet βcells of type 2 diabetic mice

WU Yan-ju; GUAN Yi-fu

doi:10.3969/j.issn.1002-266X.2015.20.005

Abstract：Objective To investigate the effect of sitagliptin treatment on the expression of autophagy related genes Atg3, Atg12 and Beclin1 in the islet βcells of type 2 diabetic mice.Methods Thirty nine-month-old male db/db mice were randomly divided into two groups , mice in the sitagliptin treatment group ( DT group ) were intragastrically adminis-tered with sitagliptin (80 mg/kg), and mice in the diabetic control group (DC group) were administered with the same a-mount of water .All drug and water was administered once a day for five weeks .Blood glucose , plasma insulin and pancre-atic insulin content were examined .The morphology of islets was analyzed by immunofluorescence .The mRNA expression of Atg3, Atg12 and Beclin1 in the isletβcells was determined by real-time fluorescent quantitative PCR .The expression of Beclin1 protein was examined by immunohistochemistry .The caspase3 activity in the islet βcells was analyzed by commer-cial kit.Results After five-week treatment with sitagliptin , the blood glucose levels in the DT group were lower than those of the DC group (P<0.01), and plasma insulin and pancreatic insulin content were increased significantly in the DT group as compared with those of the DC group (all P<0.01).Theαcells in the DC group distributed to the whole islets with higher proportion , and βcells in the DT group mainly located in the center of islet with high proportion .The mRNA expression of Atg3, Atg12 and Beclin1 in the DT group was significantly decreased as compared with that of the DC group (all P<0.01), and the Beclin1 protein expression was decreased in the DT group as compared with that of the DC group (P<0.01).Conclusion Sitagliptin inhibits the islet βcell apoptosis and improves islet structure and βcell function by down-regulating the expression of Atg3, Atg12 and Beclin1 in the islet βcells of type 2 diabetic mice.