The effect of metformin along with high-intensity interval training on gene expression of FoxO1 and Atrogin-1 in type 2 diabetic mice

Background and aims: Muscle atrophy is a complication of type 2 diabetes, in which the expression of atrophy-related genes is increased. The present study aimed to investigate the effect of high-intensity interval training (HIIT) and metformin on gene expression of two atrophy-related genes (i.e., FoxO1 and Atrogin-1) in the skeletal muscle of diabetic mice. Methods: A total of 30 mice (C57BL/6) were assigned to two groups: control (n=6), and high-fat diet (HFD) (n=24). The mice in the HFD group were fed a HDF for 16 weeks. Then, diabetes was induced in mice by HFD. Then, they were divided into 4 groups as follows: (i) diabetic control, (ii) diabetes + metformin (DM), (iii) diabetes + HIIT (DH), and (iv) diabetes + metformin + HIIT (DMH). The DM group took metformin, the HIIT group performed a HIIT program, and the DMH group had both HIIT and metformin. The real-time PCR methods were used to measure the mRNA expression of FoxO1 and Atrogin-1. Results: The findings showed that HFD-induced diabetes caused increases in the expression of FoxO1 (P=0.0006) and Atrogin-1 (P=0.0008), and HIIT could restrain these increments (P=0.086, P=0.041). However, the decreasing effect of metformin on the expression of these genes was not significant (P=0.15) and the combined effect of HIIT and metformin on the expression of these genes was not greater than the individual effect of HIIT (P=0.64). Conclusion: These results indicated that HIIT (but not metformin) may prevent type 2 diabetes-induced downregulation of FoxO1 and Atrogin-1 in skeletal muscle, and metformin could not affect the impact of the training on these atrophy-related genes.