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. Author manuscript; available in PMC: 2012 Jul 18.
Published in final edited form as: Clin Sci (Lond). 2012 Mar;122(6):253–270. doi: 10.1042/CS20110386

Figure 2. Potential molecular mechanisms of metformin action on hepatic gluconeogenesis.

Figure 2

After hepatic uptake through OCT1, the mitochondria is the primary target of metformin which exerts specific and AMPK-independent inhibition of respiratory-chain complex 1. The resultant mild decrease in energy status leads to acute and transient inhibition of energy-consuming gluconeogenic pathway. In addition, through AMPK-dependent and -independent regulatory points, metformin can lead to the inhibition of glucose production by disrupting gluconeogenesis gene expression. In parallel, the LKB1-dependent activation of AMPK triggered by ATP depletion could reduce hepatic lipogenesis and exert an indirect effect on hepatic insulin sensitivity to control hepatic glucose output.