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Metformin activates adenosine-monophosphate-activated protein kinase (AMPK), which phosphorylates the target of rapamycin complex 2 (TORC2), thereby blocking its nuclear translocation and transcription of the genes involved in gluconeogenesis. Liver kinase B1 (LKB1) is essential for the activation of AMPK. Positive AMPK signals prevent the mitogenic activity of mammalian target of rapamycin (mTOR) C1 pathway.
