Long-term effect of metformin on the glucose metabolism and islet function in mice with gestational diabetes mellitus

Abstract:

Objective：To investigate the characteristics of glucose metabolism and the effect of metformin treatment on the insulin re－sistance and islet function in elderly mice with the history of gestational diabetes mellitus（GDM）. Methods：The mice were randomly divided into the control group（n=6），GDM group（n=6） and treatment group（n=6）. The animal model was established by high fat diet and the treatment group was administered metformin in the 11.5-17.5d of pregnancy. The body weight was monitored every month after delivery. Nine months after delivery，oral glucose tolerance test（OGTT） and insulin tolerance test（ITT） were adopted to detect the glucose metabolism in elderly mice with GDM history. The pathological changes of islets were observed under HE staining，and the expression of Ki67 in pancreatic tissues was detected by immunohistochemical staining. Results：Two months after delivery，the body weights of GDM and treatment group increased significantly（F=3.875，P=0.044） compared with the control. In GDM group，Glucose decreased slowly after intraperitoneal injection of insulin（P=0.004），islet shrank and the number of islets decreased. The expression of Ki67 was strongly positive in the islets of the control group（P=0.032）. Conclusion：For mice with GDM，blood glucose can return to be normal after delivery，but insulin resistance persists. For the elderly mice with GDM history，the islets present atrophy，function de－generates gradually，and the proliferation ability decreases. Metformin treatment during pregnancy can reverse the elderly insulin re－sistance and improve the pathological changes of islets，but can not change the proliferation ability.