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Temporal coding of insulin action through multiplexing of the AKT pathway

Kubota H, Noguchi R, Toyoshima Y, Ozaki YI, Uda S, Watanabe K, Ogawa W, Kuroda S · 2012 · Molecular Cell · Atlas ID KUB2012

What this study shows

The same pathway can carry different messages in the shape of its signal over time. A short insulin pulse produced transient AKT phosphorylation and a sustained dose produced sustained AKT phosphorylation. S6K read only the transient part, G6Pase only the sustained part and GSK3-beta both. Which output responds depends on the pattern, not just the amount - the clearest cell-level case in the atlas that timing carries information in this pathway.

Abstract

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One of the unique characteristics of cellular signaling pathways is that a common signaling pathway can selectively regulate multiple cellular functions of a hormone; however, this selective downstream control through a common signaling pathway is poorly understood. Here we show that the insulin-dependent AKT pathway uses temporal patterns multiplexing for selective regulation of downstream molecules. Pulse and sustained insulin stimulations were simultaneously encoded into transient and sustained AKT phosphorylation, respectively.

Read the full abstract on PubMed →

At a glance

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Evidence type M Molecular — cells, biochemistry, structure Marked M because it is molecular or in-vitro work (model: Rat hepatoma cells (Fao); pulse vs sustained insulin, time-course phosphorylation plus kinetic modelling) 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 systemRat hepatoma cells (Fao); pulse vs sustained insulin, time-course phosphorylation plus kinetic modelling
JournalMolecular Cell
Year2012
Peer reviewedYes
Record last updated2026-10-01
SourceDOI 10.1016/j.molcel.2012.04.018 · PMID 22633957

Where this study fits

How this study connects to the pathway map, open questions, people and other studies in the Atlas.

People in the Atlas

  • Hiroyuki Kubota first author · 2 studies in the Atlas

    Systems biologist who showed that the insulin pathway carries different messages in the timing of its signal, and that S6K, the mTORC1 target, reads only the fast part

  • Shinya Kuroda last author · 2 studies in the Atlas

    Leads a systems biology lab that studies how cells decode the timing of hormone signals, with insulin and mTORC1-S6K as the main test case

  • Shinsuke Uda 2 studies in the Atlas

    Systems biologist who uses information theory and modelling. He co-authored the studies showing that the insulin–AKT pathway encodes insulin’s timing pattern, and that S6K, downstream of mTORC1, reads only the fast, pulse-like part.

More: 5 other authors

No profile yet: Noguchi R, Toyoshima Y, Ozaki YI, Watanabe K, Ogawa W

Related studies

More related studies

All 212 studies on mTORC1

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.

InterventionPulse versus sustained insulin stimulation
TargetAKT; S6K; G6Pase; GSK3-beta
ModelRat (hepatoma cell line)
EffectS6K selectively decodes transient AKT signalling; G6Pase decodes sustained; GSK3-beta decodes both

Cite this paper

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Kubota, H., Noguchi, R., Toyoshima, Y., Ozaki, Y. I., Uda, S., Watanabe, K., Ogawa, W., & Kuroda, S. (2012). Temporal coding of insulin action through multiplexing of the AKT pathway. Molecular Cell. https://doi.org/10.1016/j.molcel.2012.04.018

@article{KUB2012,
  author       = {Kubota, H. and Noguchi, R. and Toyoshima, Y. and Ozaki, Y. I. and Uda, S. and Watanabe, K. and Ogawa, W. and Kuroda, S.},
  title        = {{Temporal coding of insulin action through multiplexing of the AKT pathway}},
  journal      = {Molecular Cell},
  year         = {2012},
  doi          = {10.1016/j.molcel.2012.04.018},
  note         = {PMID: 22633957},
}

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 KUB2012) [Data set]. https://mtor-atlas.org/study/KUB2012/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_KUB2012,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record KUB2012},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/KUB2012/},
  doi          = {10.5281/zenodo.22059963}
}
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