The role of myostatin signaling pathway in improvement of skeletal muscle atrophy in type 2 diabetic rats after 4 weeks of eccentric endurance exercise

doi:10.12047/j.cjap.5632.2018.053

Abstract

Abstract: Objective: To observe the effect of 4 weeks eccentric endurance exercise on metabolic disturbance and muscle atrophy in type 2 diabetic rats, and to investigate the role of myostatin/Smad3/atrogin-1 signaling pathway in muscle atrophy.Methods: Type 2 diabetic rats were established by high fat diet combined with streptozotocin(STZ) injection for 9 weeks. The normal chow diet rats were randomly divided into control group (C, n=6) and exercise group (E, n=9), the type 2 diabetic mellitus rats were randomly divided into diabetic control group (D, n=8) and diabetic exercise group (DE, n=12). Exercise program:slope of -5°, speed of 16 m/min, 60 min each time, 1 time a day, 5 d per week for 4 weeks. Fasting blood glucose (FBG), fasting insulin (FINS), insulin resistance index (homeostasis model assessment insulin resistance index, HOMA-IR), insulin sensitivity index (insulin sensitivity index, ISI) and glucose tolerance test were measured on fasting 12 hours after exercise. Soleus muscle was drawed after exercise and the degree of muscle atrophy was detected. The expressions of myostatin, phospho-Smad3 (p-Smad3), drosophila mothers against decapentaplegic protein 3 (Smad3) and atrogin-1 were detected.Results: ①Compared with control group, body weight, soleus mass/tibia length, muscle fiber cross-sectional area, FINS and ISI of diabetic group rat were decreased significantly (P<0.01), FBG, HOMA-IR, area under the curve of blood glucose (AUC_BG), the expression of all myostatin, Smad3, p-Smad3 and atrogin-1 was increased significantly (P<0.01). ②After 4 weeks of eccentric exercise, compared with diabetic group, muscle fiber cross-sectional area of diabetic exercise group rat was increased significantly(P<0.01). AUC_BG, HOMA-IR, the expression of myostatin, p-Smad3 and atrogin-1 were decreased significantly (P<0.05, P<0.01).Conclusion: The up-regulation of myostatin/Smad3/atrogin-1 signaling 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 ameliorate metabolic disorders and increase insulin sensitivity in type 2 diabetes.

Key words: eccentric endurance exercise, type 2 diabetes, rat, muscle atrophy, myostatin

WANG Ji, ZHOU Yue, ZHANG He, LI Wen-bo, HUANG Yi. The role of myostatin signaling pathway in improvement of skeletal muscle atrophy in type 2 diabetic rats after 4 weeks of eccentric endurance exercise[J]. CJAP, 2018, 34(3): 223-228.

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