Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice

Pende M, Kozma SC, Jaquet M, Oorschot V, Burcelin R, Le Marchand-Brustel Y, Klumperman J, Thorens B, Thomas G · 2000 · Nature · Atlas ID PEN2000

What this study shows

Mice lacking S6 kinase 1 had low blood insulin and were glucose intolerant. Isolated muscle from these mice did not show insulin resistance; instead, glucose-stimulated insulin secretion and pancreatic insulin content were sharply reduced. Glucose sensing and insulin production per se were intact: the defect was a smaller pancreatic endocrine mass, explained by a selective decrease in beta-cell size. The authors noted that the phenotype resembles preclinical type 2 diabetes in which poor nutrition early in life leads to low insulin. Boundary: Mouse genetic knockout with lifelong S6K1 loss. Not tested in people. Drafted from the abstract only.

Abstract

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Insulin controls glucose homeostasis by regulating glucose use in peripheral tissues, and its own production and secretion in pancreatic beta cells. These responses are largely mediated downstream of the insulin receptor substrates, IRS-1 and IRS-2 (refs 4-8), through distinct signalling pathways. Although a number of effectors of these pathways have been identified, their roles in mediating glucose homeostasis are poorly defined.

Read the full abstract on PubMed →

At a glance

Evidence type	A Animal model Marked A because it is an animal intervention or observation study measuring an organismal outcome (model: S6K1 knockout mice; isolated muscle insulin sensitivity; pancreatic islet morphometry and insulin secretion); the code names the system studied -- animal work can be rigorous and still not be human data.
Study type	4 - Animal Study
Model system	S6K1 knockout mice; isolated muscle insulin sensitivity; pancreatic islet morphometry and insulin secretion
Journal	Nature
Year	2000
Peer reviewed	Yes
Record last updated	2026-10-01
Source	DOI 10.1038/35050135 · PMID 11140689

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	Germline S6K1 knockout
Target	Beta-cell size, insulin secretion, glucose tolerance
Model	Mouse
Effect	Loss of S6K1 reduces beta-cell size and insulin output, causing glucose intolerance

In the Atlas

Cite this paper

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Pende, M., Kozma, S. C., Jaquet, M., Oorschot, V., Burcelin, R., Le Marchand-Brustel, Y., Klumperman, J., Thorens, B., & Thomas, G. (2000). Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice. Nature. https://doi.org/10.1038/35050135

@article{PEN2000,
  author       = {Pende, M. and Kozma, S. C. and Jaquet, M. and Oorschot, V. and Burcelin, R. and Le Marchand-Brustel, Y. and Klumperman, J. and Thorens, B. and Thomas, G.},
  title        = {{Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice}},
  journal      = {Nature},
  year         = {2000},
  doi          = {10.1038/35050135},
  note         = {PMID: 11140689},
}

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 PEN2000) [Data set]. https://mtor-atlas.org/study/PEN2000/ · Dataset DOI 10.5281/zenodo.22059963

@misc{atlas_PEN2000,
  author       = {Barton, Oliver},
  title        = {{Oliver's mTOR Atlas}, record PEN2000},
  howpublished = {Data set},
  year         = {2026},
  url          = {https://mtor-atlas.org/study/PEN2000/},
  doi          = {10.5281/zenodo.22059963}
}

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