Oliver's mTOR Atlas Evidence Platform
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Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity

Lamming DW, Sabatini DM · 2012 · Science · Atlas ID LAM2012

What this study shows

In mice, chronic rapamycin also disrupts mTORC2, causing insulin resistance; lifespan extension can be uncoupled from this side effect.

Abstract

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Rapamycin, an inhibitor of mechanistic target of rapamycin complex 1 (mTORC1), extends the life spans of yeast, flies, and mice. Calorie restriction, which increases life span and insulin sensitivity, is proposed to function by inhibition of mTORC1, yet paradoxically, chronic administration of rapamycin substantially impairs glucose tolerance and insulin action. We demonstrate that rapamycin disrupted a second mTOR complex, mTORC2, in vivo and that mTORC2 was required for the insulin-mediated suppression of hepatic gluconeogenesis.

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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 (in vivo glucose and insulin tolerance)); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type4 - Animal Study
Model systemMouse (in vivo glucose and insulin tolerance)
JournalScience
Year2012
Peer reviewedYes
Record last updated2026-07-29
SourceDOI 10.1126/science.1215135 · PMID 22461615 · Free full text (PMC3324089)

Extracted findings

InterventionRapamycin (chronic)
TargetmTORC1 vs mTORC2
ModelMouse
EffectIn mice, chronic rapamycin causes insulin resistance via disruption of mTORC2, uncoupled from its longevity effect

In the Atlas

Related topics

RapamycinmTORC2Insulin resistance

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Cite this paper

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Lamming, D. W., & Sabatini, D. M. (2012). Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity. Science. https://doi.org/10.1126/science.1215135

@article{LAM2012,
  author       = {Lamming, D. W. and Sabatini, D. M.},
  title        = {{Rapamycin-induced insulin resistance is mediated by mTORC2 loss and uncoupled from longevity}},
  journal      = {Science},
  year         = {2012},
  doi          = {10.1126/science.1215135},
  note         = {PMID: 22461615},
}

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 LAM2012) [Data set]. https://mtor-atlas.org/study/LAM2012/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_LAM2012,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record LAM2012},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/LAM2012/},
  doi          = {10.5281/zenodo.22059963}
}