Research
Energy balance
Metformin activates hepatic AMPK primarily by inhibiting mitochondrial complex I, leading to reduced ATP and increased AMP, which is distinct from other activators like A-769662.
Metformin works by inhibiting mitochondrial complex I, which lowers ATP and raises AMP, thereby activating AMPK. This mechanism helps reduce hepatic glucose production and improves insulin sensitivity.
GoodSupportsHIGH confidence
the direct inhibition of the respiratory chain complex 1 by the biguanide constitutes the more convincing molecular mechanism, leading to reduced cellular ATP and increased AMP.
Why this rating
Supported by multiple studies cited in the review.
Source
AMP‐activated protein kinase in the regulation of hepatic energy metabolism: from physiology to therapeutic perspectives
Benoı̂t Viollet et al. · Acta Physiologica · 2009
DOI 10.1111/j.1748-1716.2009.01970.x
narrative_reviewCited 482×
Read the paper DOI resolved against Crossref · corpus check 2026-06-10
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