HIIT Improves Insulin Resistance In T2DM Mice By Regulating Lipid Metabolism In Skeletal Muscle

Abstract

Abnormal skeletal muscle lipid metabolism is associated with insulin resistance in people with type 2 diabetes. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose and improves insulin resistance in individuals with type 2 diabetes. However, the physical mechanism is largely unknown. PURPOSE: This study aimed to investigate whether HIIT improves insulin resistance in T2DM mice by regulating lipid metabolism in skeletal muscle. METHODS: Diabetic mice were randomly assigned to the diabetes group (T2DM, n=11) and the HIIT group (n=11), and age-matched wild type mice were assigned as the control group (CON, n=11). HIIT was performed on a motored mice treadmill at 15° inclination 5 days/week for 8 weeks. The mice were trained with a starting speed of 10m/min, where after HIIT consisted of 10 bouts of 4 min high-intensity treadmill running, interspersed by 2 min complete rest. The pace during HIIT was increased gradually from 16 to 26 m/min over eight weeks. The fasting blood glucose, glucose tolerance was measured one week before the end of the experiment, and the gastrocnemius muscles of mice were collected 36h after the last exercise. The fat content of skeletal muscle was detected by Oil Red O staining. Protein expression of ACC, HMGCR, Cpt-1α, and CD36 was measured with Western blot. RESULTS: The fasting blood glucose was decreased in the HIIT mice when compared to that in the T2DM mice (17.6±0.72 vs. 19.8±0.74 mmol/L, p<0.01). Glucose tolerance and the area under the curve (3325±126.4 vs. 3737±38. mmol/L·min, p<0.01) were improved after HIIT treatment when compared to that in the T2DM mice. Skeletal muscle exhibited a substantial amount of lipid deposition in the T2DM group, which was markedly alleviated in the HIIT group (p<0.05). In the skeletal muscle, HIIT treated mice showed significantly decreased protein expression related to lipogenesis, including reductions in ACC (0.39-fold, p<0.01) and HMGCR (0.52-fold, p<0.01). Expectedly, the protein expression level of Cpt-1α (1.6-fold, p<0.01) and CD36 (1.78-fold, p<0.01) was significantly enhanced by HIIT. CONCLUSION: HIIT improves insulin resistance was, at least partly, through deduces lipogenesis and increases lipolysis in skeletal muscle in the T2DM mice.