Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state

Foretz M, Hebrard S, Leclerc J, Zarrinpashneh E, Soty M, Mithieux G, Sakamoto K, Andreelli F, Viollet B · 2010 · The Journal of Clinical Investigation · Atlas ID FOR2010

What this study shows

The paper that broke the simple 'metformin works through AMPK' story. Metformin still suppressed hepatic glucose production in mice and hepatocytes lacking AMPK or LKB1, acting instead through a fall in hepatic energy charge. Any claim that metformin's benefit is AMPK-mediated has to answer this result.

Abstract

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Metformin is widely used to treat hyperglycemia in individuals with type 2 diabetes. Recently the LKB1/AMP-activated protein kinase (LKB1/AMPK) pathway was proposed to mediate the action of metformin on hepatic gluconeogenesis. However, the molecular mechanism by which this pathway operates had remained elusive. Surprisingly, here we have found that in mice lacking AMPK in the liver, blood glucose levels were comparable to those in wild-type mice, and the hypoglycemic effect of metformin was maintained.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: Mouse (liver-specific AMPK-null and LKB1-null); primary hepatocytes); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	Mouse (liver-specific AMPK-null and LKB1-null); primary hepatocytes
Journal	The Journal of Clinical Investigation
Year	2010
Peer reviewed	Yes
Record last updated	2026-07-29
Source	DOI 10.1172/JCI40671 · PMID 20577053

Extracted findings

These fields were extracted from the paper with AI assistance and have not been checked against the source. Read them as a pointer into the paper, not as curated claims; where they disagree with the curated summary above, the curated summary stands.

Intervention	Metformin in AMPK-null / LKB1-null mouse liver
Target	Hepatic energy state (AMPK-independent)
Model	Mouse
Effect	Metformin suppresses hepatic gluconeogenesis without AMPK or LKB1, via reduced hepatic energy charge

In the Atlas

Cite this paper

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Foretz, M., Hebrard, S., Leclerc, J., Zarrinpashneh, E., Soty, M., Mithieux, G., Sakamoto, K., Andreelli, F., & Viollet, B. (2010). Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state. The Journal of Clinical Investigation. https://doi.org/10.1172/JCI40671

@article{FOR2010,
  author       = {Foretz, M. and Hebrard, S. and Leclerc, J. and Zarrinpashneh, E. and Soty, M. and Mithieux, G. and Sakamoto, K. and Andreelli, F. and Viollet, B.},
  title        = {{Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state}},
  journal      = {The Journal of Clinical Investigation},
  year         = {2010},
  doi          = {10.1172/JCI40671},
  note         = {PMID: 20577053},
}

Cite this Atlas record

The record is the Atlas's own work — the evidence label, the extracted findings and the links. It is cited as part of the dataset, not as the paper.

Barton, O. (2026). Oliver's mTOR Atlas (record FOR2010) [Data set]. https://mtor-atlas.org/study/FOR2010/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_FOR2010,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record FOR2010},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/FOR2010/},
  doi          = {10.5281/zenodo.22059963}
}

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