As the most commonly used oral hypoglycemia agent worldwide,27,28 metformin activates AMPK by increasing cellular ratio of AMP to ATP through inhibiting mitochondrial respiration and adenosine triphosphate production.27 Given that AMPK is a key regulator in metabolic diseases and a potential target for the treatment of diabetes mellitus, and the above synergistic effects we saw with the combination of metformin and IHMT-MST1-39, we investigated whether IHMT-MST1-39 itself is involved in the regulation of metabolic status by activating AMPK. Here, MST1 is linked to metabolic disease.