Mechanisms of action of metformin in type 2 diabetes: Effects on mitochondria and leukocyte-endothelium interactions.
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"Mechanisms of action of metformin i..." refers background in this paper
...macrovascular complications such as myocardial ischaemia and stroke [6]....
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"Mechanisms of action of metformin i..." refers background in this paper
...Importantly, the NADH dehydrogenase of the complex I ubiquinone oxidoreductase and complex III cytochrome c reductase are the two main sites of O2 production via the ETC [3]....
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...Hyperglycaemia and hyperlipidemia enhance glucose and lipid catabolism, leading to increased production of NADH and FADH2, which are used by the mitochondrial electron transport chain (ETC) to generate ATP [48]....
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...The mitochondrial interference of metformin seems to occur beyond ETC complex I....
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...Metformin-mediated ETC complex I inhibition (revised below) suppresses ATP production, which leads to an increase in cellular AMP and ADP levels and alters the AMP/ATP ratio....
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...Although the molecular mechanisms of its actions in skeletal muscle and liver and its vasoprotective effects are yet to be clarified, it seems that oxidative stress and mitochondrial function are secondary to an action that takes place at the ETC, specifically in complex I....
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5,146 citations
"Mechanisms of action of metformin i..." refers background in this paper
...the activation of AMPK through the energetic dysbalance (increased AMP/ATP ratio), metformin has been reported to activate AMPK by increasing phosphorylation of the AMPK catalytic α subunit at Thr172 in primary hepatocytes [112]....
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