Combination of imeglimin and resistance exercise improves mitochondrial function and glucose metabolism in skeletal muscles

The diabetes medication imeglimin, which operates through a novel mechanism of action and resistance training (RT), a significant exercise therapy, effectively enhances mitochondrial function in skeletal muscles and regulates blood glucose levels. However, the efficacy of the combination therapy remains unclear. The combination of imeglimin and RT enhanced mitochondrial function, reduced inflammatory cytokine levels, and upregulated the expression of anti-inflammatory and antioxidant-related genes as determined by RT-PCR. Additionally, there was an increase in the protein expression of peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1-α), a crucial regulator of mitochondrial biogenesis and glucose metabolism. This was accompanied by elevated levels of sirtuins (Sirt) 1 and 3, which positively regulate PGC1-α activity, as well as an increase in nicotinamide adenine dinucleotide (NAD + ) levels, which are involved in Sirt1 and Sirt3 activity. Furthermore, an increase in the phosphorylation rate of protein kinase B (Akt), which plays a role in insulin signaling, and upregulation of glucose transporter type 4 (GLUT4), which is involved in glucose uptake, were observed. These findings suggest that the combination of imeglimin and RT is a promising therapeutic approach to enhance mitochondrial function and glucose metabolic capacity. • Imeglimin combined with resistance training enhanced mitochondrial function and reduced inflammation in skeletal muscle. • This combination also increase PGC1-α, Sirt 1 and Sirt 3 protein expressions, and enhanced insulin sensitivity • This could be a promising therapeutic approach to enhance mitochondrial function and glucose metabolic capacity.