Evidence mapPaperPMID 28089566Full record

ArticleCell metabolism2017

Metformin Inhibits Hepatic mTORC1 Signaling via Dose-Dependent Mechanisms Involving AMPK and the TSC Complex.

Jessica J Howell, Kristina Hellberg, Marc Turner, George Talbott, Matthew J Kolar, Debbie S Ross, Gerta Hoxhaj, Alan Saghatelian, Reuben J Shaw, Brendan D Manning

Open access · bronzeAbstract read
In one paragraph

Article in Cell metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
237citing papers in PubMed, 6 pooled it
16.5field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

237 citing papers in PubMed, 6 syntheses or guidelines pooled it, 395 citations in OpenAlex.

  1. Pooled it
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  7. Favorable Antiviral Effect of Metformin on SARS-CoV-2 Viral Load in a Randomized, Placebo-Controlled Clinical Trial of COVID-19.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2024
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177 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

10 authors at 2 institutions in 1 country.

Jessica J HowellDepartment of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Kristina HellbergMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Marc TurnerDepartment of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
George TalbottDepartment of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Matthew J KolarClayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Debbie S RossMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Gerta HoxhajDepartment of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
Alan SaghatelianClayton Foundation Laboratories for Peptide Biology, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Reuben J ShawMolecular and Cell Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA. Electronic address: shaw@salk.edu.
Brendan D ManningDepartment of Genetics and Complex Diseases, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA. Electronic address: bmanning@hsph.harvard.edu.
Harvard University · USSalk Institute for Biological Studies · US

Funding

Viral Vector Core (VVC)P30CA014195 · NCI · SALK INSTITUTE FOR BIOLOGICAL STUDIES · 1985 to 2025
$37.5M
MEDICAL SCIENTIST TRAINING PROGRAMT32GM007198 · UNIVERSITY OF CALIFORNIA SAN DIEGO · 1985 to 2005
$5.4M
Project 3: Identifying transcriptional driver genes and targeting transcription in TSCP01CA120964 · BRIGHAM AND WOMEN'S HOSPITAL · 2025 to 2025
$2.1M
Decoding and Targeting the PI3K-mTOR Signaling Network in CancerR35CA197459 · HARVARD UNIVERSITY D/B/A HARVARD SCHOOL OF PUBLIC HEALTH · 2025 to 2025
$960k
NCI NIH HHS P01 CA120964NCI NIH HHS P30 CA014195NCI NIH HHS R01 CA172229NCI NIH HHS R35 CA197459NIDDK NIH HHS F30 DK112604NIDDK NIH HHS F32 DK095508NIDDK NIH HHS R01 DK080425NIGMS NIH HHS T32 GM007198
6 · The paper itself

Abstract

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. Here we show that metformin robustly inhibits mTORC1 in mouse liver tissue and primary hepatocytes. Using mouse genetics, we find that at the lowest concentrations of metformin that inhibit hepatic mTORC1 signaling, this inhibition is dependent on AMPK and the tuberous sclerosis complex (TSC) protein complex (TSC complex). Finally, we show that metformin profoundly inhibits hepatocyte protein synthesis in a manner that is largely dependent on its ability to suppress mTORC1 signaling.

Indexed as

AMP-Activated Protein KinasesAnimalsDose-Response Relationship, DrugHepatocytesHumansLiverMechanistic Target of Rapamycin Complex 1MetforminMice, Inbred C57BLMice, KnockoutMultiprotein ComplexesOrgan SpecificityProtein BiosynthesisSignal TransductionTOR Serine-Threonine KinasesTuberous SclerosisAMP-Activated Protein KinasesMechanistic Target of Rapamycin Complex 1MetforminMultiprotein ComplexesTOR Serine-Threonine KinasesAMPKhepatocyteslivermetforminmTORmTORC1protein synthesisTSC1TSC2tuberous sclerosis complex

Identifiers

PMID28089566
PMCPMC5299044
OpenAlexW2572741715

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.