Oliver's mTOR Atlas Evidence Platform
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Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex

Howell JJ, Hellberg K, Turner M, Talbott G, Kolar MJ, Ross DS, Hoxhaj G, Saghatelian A, Shaw RJ, Manning BD · 2017 · Cell Metabolism · Atlas ID HOW2017

What this study shows

Pinned down HOW the diabetes drug metformin - a major longevity candidate - actually reaches mTOR. In the liver, metformin lowers cellular energy, and at low doses this shuts down mTORC1 specifically through AMPK and the TSC complex. Direct mechanistic bridge between a widely-used drug, energy sensing, and the mTOR pathway.

Abstract

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Metformin is the most widely prescribed drug for the treatment of type 2 diabetes. However, knowledge of the full effects of metformin on biochemical pathways and processes in its primary target tissue, the liver, is limited. One established effect of metformin is to decrease cellular energy levels. The AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) are key regulators of metabolism that are respectively activated and inhibited in acute response to cellular energy depletion.

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At a glance

Evidence type M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Mouse liver + primary hepatocytes) 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 type5 - Mechanistic / In Vitro
Model systemMouse liver + primary hepatocytes
JournalCell Metabolism
Year2017
Peer reviewedYes
Record last updated2026-08-22
SourceDOI 10.1016/j.cmet.2016.12.009 · PMID 28089566 · Free full text (PMC5299044)

Extracted findings

InterventionMetformin (dose-dependent)
TargetAMPK / TSC / Rag / mTORC1
ModelMouse liver + primary hepatocytes
EffectMetformin inhibits hepatic mTORC1 via dose-dependent AMPK- and TSC-complex-dependent mechanisms

In the Atlas

Related topics

TSC1/TSC2MetforminmTORC1AMPK

Open questions that cite this study

More studies on this topic

Cite this paper

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Howell, J. J., Hellberg, K., Turner, M., Talbott, G., Kolar, M. J., Ross, D. S., Hoxhaj, G., Saghatelian, A., Shaw, R. J., & Manning, B. D. (2017). Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex. Cell Metabolism. https://doi.org/10.1016/j.cmet.2016.12.009

@article{HOW2017,
  author       = {Howell, J. J. and Hellberg, K. and Turner, M. and Talbott, G. and Kolar, M. J. and Ross, D. S. and Hoxhaj, G. and Saghatelian, A. and Shaw, R. J. and Manning, B. D.},
  title        = {{Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex}},
  journal      = {Cell Metabolism},
  year         = {2017},
  doi          = {10.1016/j.cmet.2016.12.009},
  note         = {PMID: 28089566},
}

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 HOW2017) [Data set]. https://mtor-atlas.org/study/HOW2017/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_HOW2017,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record HOW2017},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/HOW2017/},
  doi          = {10.5281/zenodo.22059963}
}