Abstract: BACKGROUND: Obesity and its relevant chronic inflammation are important risk factors for inducing type 2 diabetes. This inflammatory response will further involve skeletal muscle, leading to an increase in catabolic and autophagic fluxes in skeletal muscle. Aerobic exercise is the mainstream mode of exercise in the prevention and treatment of type 2 diabetes, and may also has a certain protective effect on skeletal muscle.
OBJECTIVE: To explore the effects and regulatory mechanisms of aerobic exercise on glucolipid metabolism, skeletal muscle inflammation and autophagy in type 2 diabetic rats.
METHODS: Animal models of type 2 diabetes were established in rats by 8-week high-fat feeding combined with streptozotocin injection, and the experimental rats were then divided into normal control group, normal exercise group, diabetic control group and diabetic exercise group. The exercise group performed 4 weeks of aerobic exercise (16 m/min, 60 min/d, 5 d/wk). The levels of blood glucose, high-density lipoprotein, low-density lipoprotein and triglyceride in serum were measured by an automated biochemical analyzer. Serum insulin level was determined using enzyme-linked immunosorbent assay and the insulin resistance index and area under the glucose metabolism curve were calculated. The levels of interleukin 6 and tumor necrosis factor α in skeletal muscle were measured by enzyme-linked immunosorbent assay after 4 weeks of aerobic exercise, and the expression levels of forkhead box protein O3 (FoxO3), LC3 and p62 in skeletal muscle were measured by western blot assay.
RESULTS AND CONCLUSION: The area under the glucose tolerance curve and insulin resistance index both increased significantly in type 2 diabetic rats (P < 0.001, P=0.025), and aerobic exercise significantly reduced the area under the glucose tolerance curve and insulin resistance index in the normal exercise group (P < 0.001, P=0.038) and diabetic exercise group (P < 0.001, P=0.004). Serum high-density lipoprotein significantly decreased (P=0.030), and low-density lipoprotein and triglyceride (P=0.027, P=0.014) levels significantly increased in the diabetic control group compared with the normal control group. Aerobic exercise significantly reduced triglyceride and low-density lipoprotein levels in the normal exercise group (P=0.019, P=0.008) as well as triglyceride levels in the diabetic exercise group (P=0.022). Both interleukin-6 and tumor necrosis factor α levels were significantly increased in the skeletal muscle of type 2 diabetic rats compared with the normal control group (P < 0.001, P=0.007), and aerobic exercise significantly reduced tumor necrosis factor α levels in the diabetic exercise group (P=0.017). The LC3-II/LC3-I was significantly increased in the skeletal muscle of type 2 diabetic rats compared with the normal control group. Aerobic exercise significantly increased the LC3-II/LC3-I in the normal exercise group (P < 0.001) and decreased the LC3-II/LC3-I, FoxO3 and p62 protein expression levels in the diabetic exercise group (P=0.026, P=0.050, P=0.048). To conclusion, type 2 diabetes model established by high-fat feeding combined with streptozotocin injection has obvious glycolipid metabolism disorder, and leads to inflammatory response and excessive activation of autophagy in skeletal muscle. Aerobic exercise can improve glycolipid metabolism, reduce local inflammation in skeletal muscle and inhibit autophagy, and finally play a protective role in skeletal muscle.

Key words: type 2 diabetes, aerobic exercise, glycolipid metabolism, skeletal muscle, inflammation, autophagy