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. Author manuscript; available in PMC: 2014 Nov 4.
Published in final edited form as: J Clin Exp Pathol. 2012 May 17;Suppl 4:7327. doi: 10.4172/2161-0681.S4-002

Figure 3. Metformin.

Figure 3

Metformin inhibits complex I of the electron transport chain, leading to a rise in intracellular AMP and activation of AMPK [131,132]. AMPK activation can inhibit mTORC1 activity via phosphorylation of TSC2 [136] and Raptor [137] but metformin also independently inhibits the Rag family of GTPases that regulate mTORC1 localization [139]. Notably, the suppression of hepatic glucose output by metformin was recently shown to be dependent on reduced energy charge, but independent of AMPK [133]. Metformin further enhances insulin sensitivity directly at the level of the insulin receptor [128] and likely has indirect effects through mTORC1 by regulating the stability of IRS1/2 and Grb10.