Combined intervention of swimming plus metformin ameliorates the insulin resistance and impaired lipid metabolism in murine gestational diabetes mellitus

Gestational diabetes mellitus (GDM) has short- and long- term influence on pregnant women and fetus. Swimming, as an aerobic exercise, can effectively improve the blood glucose level in GDM, but the effect of mild swimming alone was not very substantial. Metformin, as an oral antidiabetic drug, has obvious hypoglycemic effect, and is economic also, but the long-term effect on pregnant women and fetus has not been completely clear. We hypothesize that combined intervention of mild swimming and low dose of metformin, may effectively reduce blood glucose, improve the pregnancy outcomes in GDM dams, but simultaneously avoiding the adverse effects caused by overdose of drug and impotence of mild swimming. The streptozotocin was used to stimulate C57BL/6J mice to develop GDM, by which serum glucose, TC, TG, LDL-C were increased significantly, meanwhile HDL-C was decreased significantly in the GDM control (DC) group compared with the normal control group. Swimming or metformin intervention slightly or moderately improves hyperglycemia, insulin sensitivity and lipid metabolism both in liver and skeletal muscle from GDM mice, while combined therapy of swimming plus metformin markedly ameliorated hyperglycemia (FPG, decreased by 22.2–59.5% from G10 to G18 versus DC group), insulin sensitivity (2.1 and 2.8 fold increase, respectively, in AKT activity versus DC group) and de novo lipogenesis (3.2 and 7.0 fold decrease, respectively, in ACC activity, and 1.94 and 5.1 fold decrease, respectively, in SREBP2 level, versus DC group) both in liver and skeletal muscle from GDM mice. We conclude that the combined intervention by metformin plus swimming may be more effective than single action to ameliorate glucose and lipid metabolism via improving insulin sensitivity in GDM mice.