Effects Of Moderate Swimming Exercise On Skeletal Muscle Autophagy And Glucose Metabolism In Type 2 Diabetic Mice

Purpose: Skeletal muscle plays an important role in diabetic glucose metabolism.In this study,KM mice were used to establish the type 2 diabetes mellitus models,and investigate the effect of moderate swimming exercise on skeletal muscle autophagy and glucose metabolism in type 2 diabetes mellitus mice.Methods:(1)Establishment of the model of type 2 diabetic mice: The model of type 2 diabetes mice was established by feeding high-fat and high-sugar diet and injecting streptozotocin(STZ,50mg/kg)for two consecutive days.The model was established by observing the changes of food intake,water intake,mice weight,fasting blood glucose and glucose tolerance.(2)To observe the effect of exercise on glucose metabolism and autophagy: Taking moderate swimming exercise as the intervention method,40 KM mice were randomly divided into 5 groups: normal control group,normal exercise group,diabetes group,diabetes exercise group and diabetes metformin group(8 mice in each group).moderate swimming exercise or metformin were given for 6 weeks.All 40 KM mice were randomly divided into 5 groups(n=10): control group,swimming group,diabetes mellitus group,diabetes swimming group,diabetes metformin group.The mice were given appropriate amount of swimming exercise or metformin for 6 weeks.The glycogen content,morphological changes and the expression of glucose transporter(GLUT4)in the gastriculus muscle of mice were determined by glycogen kit,HE staining and immunohistochemistry,respectively.Western blot and qPCR were used to determine the protein expression of skeletal muscle autophagy related proteins LC3 and P62,as well as mRNA expression of ATG7 and P62 respectively.Results:(1)Compared with the normal control group,the data of glucose metabolism showed that the glycogen content in skeletal muscle of diabetic mice decreased(P<0.05),and the expression of GLUT4 decreased significantly.The expression of GLUT4 could be increased by giving either moderate swimming exercise or metformin(P <0.05).(2)The morphological results showed that compared with the normal control group,the morphology of skeletal muscle cells in the diabetic group developed severe loose deformation,and the application of moderate swimming exercise or metformin significantly improved the pathological morphology.(3)The results of the autophagy study showed that there was no significant change in ATG7 mRNA expression in diabetic mice compared with the normal control group.After moderate exercise and metformin,ATG7 mRNA expression in mice decreased significantly(P<0.05).However,the expression of P62 mRNA in diabetic mice was higher than that in normal control group.Moderate swimming exercise or metformin treatment can significantly reduce P62 mRNA expression.The results of autophagy related protein expression showed that the LC3-?/LC3-?ratio decreased and P62 expression increased in diabetic mice.Moderate swimming or metformin therapy can increase the LC3-?/LC3-? ratio and decrease the expression of P62(P all<0.05).Conclusions:(1)Moderate swimming exercise can improve the glucose metabolism of skeletal muscle cells in type 2 diabetic mice.(2)Skeletal muscle of type 2 diabetic mice may down-regulate autophagy,and moderate swimming exercise may up-regulate autophagy.