In our study, cotreatment with metformin significantly enhanced p‐AMPK/AMPK ratio and protein expression of SIRT1 in high‐glucose‐stimulated INS‐1 cells, suggesting that the activation of AMPK/SIRT1/PGC‐1α signal pathway may exert a protective effect against diabetes. This evidence concerns the gene PPARGC1A and diabetes mellitus.