Conversely, the activation of AMPK by treatment with the pro-longevity diabetes drug metformin (Met) (50 mg/kg/day for 2 wk, intraperitoneal [IP]) significantly reduced blood glucose levels (Fig 4H and S2C Fig), induced Egr1 expression in primary rat cardiomyocytes (Fig 4I and S2B Fig), and caused a nonsignificant trend for the protection of mice against DXR toxicity (Fig 4J). This evidence concerns the gene PRKAA2 and diabetes mellitus.