The Effect Of Myostatin Signaling Pathway On Skeletal Muscle Atrophy In Type 2 Diabetic Rats After 4 Weeks Of Eccentric Endurance Exercise

Objective:To observe the effect of 4 weeks eccentric endurance exercise on muscle atrophy.And investigate the role of myostatin/Smad3/Atrogin-1 signaling pathway in muscle atrophy.Methods:Thirty-nine 6 weeks old male SD rats were randomly divided into normal chow diet group?NCD?and high fat diet group?HFD?.Type 2 diabetic rats were established by 9 weeks high fat diet combined with STZ injection.The modeling standard was fasting blood glucose?FBG??11.1mmol/L after2 weeks of STZ injection.Finally,20 rats were identified as type 2 diabetes.The normal rats were randomly divided into control group?C,n=6?and exercise group?E,n=9?,the model rats were randomly divided into diabetic control group?D,n=8?and diabetic exercise group?DE,n=12?.Fasting blood glucose?FBG?,fasting insulin?FINS?,Homeostasis model assessment insulin resistance index?HOMA-IR?,insulin sensitivity index?ISI?and glucose tolerance test were measured before and after 4weeks eccentric exercise.Soleus muscle was drawed after exercise.The distribution of Atrogin-1 was observed by immunohistochemistry,the expression of myostatin,p-Smad3,Smad and Atrogin-1 were detected by Western Blot.Results:?1?Compared with control group,body weight?P<0.01?,soleus mass/tibia length?P<0.01?,cross-sectional area?CSA?of muscle fiber?P<0.01?,FINS?P<0.01?,ISI?P<0.01?of diabetic group were decreased significantly.FBG?P<0.01?,HOMA-IR?P<0.01?,AUC_BG?P<0.01?of diabetic group were increased significantly.The expression of myostatin?P<0.01?,Smad3?P<0.01?,p-Smad3?P<0.01?,Atrogin-1?P<0.01?were increased significantly.?2?After 4 weeks of eccentric exercise,compared with control group,body weight?P<0.01?,FINS?P<0.01?,HOMA-IR?P<0.05?of exercise group were decreased significantly,ISI?P<0.01?,CSA of muscle fiber?P<0.01?were increased significantly.The expression of myostatin?P<0.01?,p-Smad3?P<0.01?,Atrogin-1?P<0.01?were decreased significantly.?3?After 4 weeks of eccentric exercise,compared with diabetic group,CSA of muscle fiber of diabetic exercise group were increased significantly?P=0.03?,AUC_BG?P<0.01?,HOMA-IR?P<0.01?were decreased significantly.The expression of p-Smad3?P<0.01?,Atrogin-1?P<0.01?were decreased significantly,and myostatin tended to decreased?P=0.13?.Conclusion:?1?Skeletal muscle atrophy is often induced in type 2 diabetes mellitus.4 weeks of eccentric endurance exercise control lipid metabolism in type 2 diabetes by increasing skeletal muscle capacity.?2?The up-regulation of myostatin/Smad3/Atrogin-1signaling pathway is an important cause of muscle atrophy in type 2 diabetes.The down-regulation of myostatin,p-Smad3,and Atrogin-1 after 4 weeks of eccentric endurance exercise may inhibit muscle atrophy,and then control metabolic disorders and increase insulin sensitivity in type 2 diabetes.