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.