Role of AMP-activated protein kinase in mechanism of metformin action

Zhou G, Myers R, Li Y, Chen Y, Shen X, Fenyk-Melody J, Wu M, Ventre J, Doebber T, Fujii N, Musi N, …, Moller DE · 2001 · J Clin Invest · Atlas ID ZHO2001

What this study shows

Metformin activates AMPK, suppressing hepatic gluconeogenesis and lipogenesis.

Abstract

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Metformin is a widely used drug for treatment of type 2 diabetes with no defined cellular mechanism of action. Its glucose-lowering effect results from decreased hepatic glucose production and increased glucose utilization. Metformin's beneficial effects on circulating lipids have been linked to reduced fatty liver. AMP-activated protein kinase (AMPK) is a major cellular regulator of lipid and glucose metabolism.

Read the full abstract on PubMed →

At a glance

Evidence type	M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Rat; hepatocytes; skeletal muscle) rather than a whole-organism health-outcome study. That is often exactly where causal biology gets established -- the code says which system the finding was shown in, and nothing about how good the work is.
Study type	5 - Mechanistic / In Vitro
Model system	Rat; hepatocytes; skeletal muscle
Journal	J Clin Invest
Year	2001
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1172/JCI13505 · PMID 11602624 · Free full text (PMC209533)

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
Target	AMPK (→ ACC; indirect mTORC1)
Model	Rat; hepatocytes; skeletal muscle
Effect	Metformin activates AMPK, explaining its glucose- and lipid-lowering effects

In the Atlas

Links in the pathway map

Supports Metformin activates AMPK
Supports Energy & cellular stress activates AMPK

Open questions that cite this study

Cited as supporting evidence for the open question Rapamycin + AMPK-axis drugs (acarbose / metformin): a male-mouse survival signal from cross-cohort comparison, untested in humans.

Cite this paper

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Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., Musi, N., Hirshman, M. F., Goodyear, L. J., & Moller, D. E. (2001). Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. https://doi.org/10.1172/JCI13505

@article{ZHO2001,
  author       = {Zhou, G. and Myers, R. and Li, Y. and Chen, Y. and Shen, X. and Fenyk-Melody, J. and Wu, M. and Ventre, J. and Doebber, T. and Fujii, N. and Musi, N. and Hirshman, M. F. and Goodyear, L. J. and Moller, D. E.},
  title        = {{Role of AMP-activated protein kinase in mechanism of metformin action}},
  journal      = {J Clin Invest},
  year         = {2001},
  doi          = {10.1172/JCI13505},
  note         = {PMID: 11602624},
}

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 ZHO2001) [Data set]. https://mtor-atlas.org/study/ZHO2001/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_ZHO2001,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record ZHO2001},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/ZHO2001/},
  doi          = {10.5281/zenodo.22059963}
}

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