As a widely used antidiabetic drug, metformin may also exert the protective effect on islet β cells from high‐glucose‐induced damage by activating autophagy and up‐regulating irisin via AMPK/SIRT1/PGC‐1α signal pathway (Figure 3), which will provide a novel theoretical evidence that inducing autophagy through activating AMPK/SIRT1/PGC‐1α signal pathway is a potential interventional strategy for the prevention and treatment of diabetes mellitus. The gene discussed is FNDC5; the disease is diabetes mellitus.