Exercise And/or Metformin Enhances Skeletal Muscle Insulin Sensitivity And Ameliorates Muscle Atrophy In Db/db Mice

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OBJECTIVE PURPOSE: The aims of this study were to investigate the effects of exercise and/or metformin on skeletal muscle atrophy and insulin sensitivity in db/db mice, providing a theoretical basis for the treatment of type II diabetes. METHODS: 8 BKS mice were set as the control group (Con), and 32 BKS-db/db mice were randomly divided into the quiet control group (db/db), the exercise intervention group (db/db + Ex), the metformin administration group (db/db + Met), and the exercise combined with metformin administration group (db/db + Ex+Met) (n = 8-10). The exercise groups were adapt to 8-week treadmill exercise with a slope of 0° for five days a week of 30-40 min daily, and the drug groups were given metformin at a dose of 300 mg/kg by gavage every day. Body weight and fasting blood glucose were monitored weekly. RESULTS: 1) The muscle cross-sectional area was remarkably lower in db/db group than that of in the Con group (550.68 ± 46.80 vs 837.84 ± 111.19μm2, P < 0.01), whereas mice in db/db + Ex exhibited significant increased muscle weight (39.46 ± 8.60 vs 31.73 ± 3.50 mg, P < 0.05) and cross-sectional area compared to db/db mice (706.42 ± 65.23μm2, P < 0.01). 2) The insulin signaling pathway PI3K-Akt and GLUT4 expression were significantly enhanced by 38.18% and 37.86% after exercise intervention alone or by 32.45% and 53.62% in exercise combination with metformin group. The insulin resistance index was markedly reduced only in the db/db + Ex+Met group, compared with the db/db mice (1.75 ± 0.39 vs 5.05 ± 3.56, P < 0.05). 3) Compare with db/db mice, MuRF1 and Atrogin-1 expression levels in skeletal muscle remarkably inhibited by 51.22% and 42.31% in db/db + Ex group, 35.37% and 39.10% in db/db + Met group and 47.56% and 35.90% in db/db + Ex+Met group, respectively (P < 0.01). CONCLUSION: 1) Exercise was more effective in improving skeletal muscle mass and increasing insulin sensitivity by up-regulating insulin signaling PI3K-Akt pathway than metformin intervention alone. 2) Independent and combined effects of exercise and metformin suppressed diabetic-induced skeletal muscle atrophy by reducing the expression levels of MuRF1 and Atrogin-1.This study was supported by the National Natural Science Foundation of China (Youth Program) (32000839); Jiangsu Graduate Research and Practice Innovation Program (KYCX22-2256).

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