The effect of metformin along with high-intensity interval training on gene expression of FoxO۱ and Atrogin-۱ in type ۲ diabetic mice

Background and aims: Muscle atrophy is a complication of type ۲ 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., FoxO۱ and Atrogin-۱) in the skeletal muscle of diabetic mice. Methods: A total of ۳۰ mice (C۵۷BL/۶) were assigned to two groups: control (n=۶), and high-fat diet (HFD) (n=۲۴). The mice in the HFD group were fed a HDF for ۱۶ weeks. Then, diabetes was induced in mice by HFD. Then, they were divided into ۴ 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 FoxO۱ and Atrogin-۱. Results: The findings showed that HFD-induced diabetes caused increases in the expression of FoxO۱ (P=۰.۰۰۰۶) and Atrogin-۱ (P=۰.۰۰۰۸), and HIIT could restrain these increments (P=۰.۰۸۶, P=۰.۰۴۱). However, the decreasing effect of metformin on the expression of these genes was not significant (P=۰.۱۵) and the combined effect of HIIT and metformin on the expression of these genes was not greater than the individual effect of HIIT (P=۰.۶۴). Conclusion: These results indicated that HIIT (but not metformin) may prevent type ۲ diabetes-induced downregulation of FoxO۱ and Atrogin-۱ in skeletal muscle, and metformin could not affect the impact of the training on these atrophy-related genes.