Hormonal
Metformin reduces hepatic glucose production primarily by inhibiting fructose-1,6-bisphosphatase (FBP1) via AMP-mediated allosteric inhibition, rather than solely through AMPK activation.
Metformin lowers blood sugar partly by directly inhibiting an enzyme (FBP1) in the liver that makes glucose, triggered by changes in cellular energy (AMP). This happens alongside its known effects on AMPK. For patients, this means metformin is effective through multiple pathways, which may explain its broad utility in type 2 diabetes management.
Here, we report that the AMP-inhibited enzyme fructose-1,6-bisphosphatase-1 (FBP1, EC 3.1.3.11), a rate-controlling enzyme in gluconeogenesis, functions as a major contributor to the therapeutic action of metformin.
Why this rating
High-quality in vivo evidence using knockin mouse models demonstrating resistance to metformin when FBP1 is AMP-insensitive.
Source
Metformin reduces liver glucose production by inhibition of fructose-1-6-bisphosphatase
Roger W. Hunter et al. · Nature Medicine · 2018
DOI 10.1038/s41591-018-0159-7
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