The Protective Effect Of Metformin On Glucose Metabolism And Long-term Complications In Mice With Gestational Diabetes Mellitus

Objective: To investigate the characteristics of glucose metabolism and the effect of metformin treatment during pregnancy on insulin resistance?islet morphology and proliferation?blood pressure levels and cognitive function in elderly mice with the history of gestational diabetes mellitus(GDM).Methods: The mice were randomly divided into LFD+Vehicle group(n = 6),HFD+Vehicle group(n = 6)and HFD+Metformin group(n =6).GDM model was established by high fat diet(HFD).Body weight were monitored every month after delivery.In 9 months after delivery,oral glucose tolerance test(OGTT)and insulin tolerance test(ITT)were measured to detect the glucose metabolism in elderly mice with the history of GDM.HE staining was used to observe the pathological changes of islets.Immunohistochemical staining was used to identify the expression of Ki67 in pancreatic tissues.The mouse noninvasive blood pressure analysis system was used to measure blood pressure level.The Morris water mazewas used to evaluate cognitive function.Results:After delivery,the body weight of HFD+Vehicle and HFD+Metformin group increased significantly compared with control.Weight gain slowed down in HFD+Metformin group in 6 months after delivery.In HFD+Vehicle group,glucose decreased slowly after intraperitoneal injection of insulin,islet shrank and the number of islets decreased,the expression of Ki67 in islets was reduced,the systolic pressure increased obviously,escape latency increased,the times and duration spent on the target quadrants were shortened.Compared with the HFD+Vehicle group,the number of islets in the HFD+Metformin group was increased,escape latency decreased,the times and duration spent on the target quadrants were extended,and there was a tendency to decrease the area under curve in ITT as well as systolic pressure.Conclusion: Blood glucose can return to normal after delivery in mice with GDM,but insulin resistance persisted.Islets atrophied,the ability of proliferation decreased,blood pressure increased and cognitive function impaired in elderly mice with the history of GDM.Treatment of metformin during pregnancy can reverse insulin resistance,the pathological changes of islets and cognitive function.It has a protective effect on the cardiovascular system.But it can not change the ability of proliferation.