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Fig. 1: Proposed mechanisms for metformin-induced reductions in blood levels of glucose. | Nature Reviews Endocrinology

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Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript. Advertisement From: Metformin: update on mechanisms of action and repurposing potential Left: Complex I inhibition-dependent mechanisms. In the liver, metformin induces a mild inhibition of mitochondrial respiratory chain complex I, leading to a moderate decrease in ATP synthesis and a concomitant increase in cellular levels of AMP. The metformin-induced decrease in hepatic gluconeogenic flux, an ATP-dependent metabolic process, could result from this reduction in ATP levels. In addition, increased AMP levels lead to inhibition of the activity of enzymes that are regulated by AMP and are involved in gluconeogenesis, such a

Left: Complex I inhibition-dependent mechanisms. In the liver, metformin induces a mild inhibition of mitochondrial respiratory chain complex I, leading to a moderate decrease in ATP synthesis and a concomitant increase in cellular levels of AMP. The metformin-induced decrease in hepatic gluconeogenic flux, an ATP-dependent metabolic process, could result from this reduction in ATP levels. In addition, increased AMP levels lead to inhibition of the activity of enzymes that are regulated by AMP and are involved in gluconeogenesis, such as adenylate cyclase and fructose-1-6-bisphosphatase…

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