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

Mario Pende, Sara C. Kozma, Muriel Jaquet, Viola Oorschot, Rémy Burcelin, Yannick Le Marchand-Brustel, Judith Klumperman, Bernard Thorens and George Thomas ()
Additional contact information
Mario Pende: Friedrich Miescher Institute
Sara C. Kozma: Friedrich Miescher Institute
Muriel Jaquet: Institute of Pharmacology and Toxicology
Viola Oorschot: University Medical Center and Research Institute of Biomembranes
Rémy Burcelin: Institute of Pharmacology and Toxicology
Yannick Le Marchand-Brustel: INSERM E 99-11, Biologie et physiologie de la Nutrition et Signalisation, Faculty of Medicine
Judith Klumperman: University Medical Center and Research Institute of Biomembranes
Bernard Thorens: Institute of Pharmacology and Toxicology
George Thomas: Friedrich Miescher Institute

Nature, 2000, vol. 408, issue 6815, 994-997

Abstract: Abstract Insulin controls glucose homeostasis by regulating glucose use in peripheral tissues, and its own production and secretion in pancreatic β cells1,2,3. These responses are largely mediated downstream of the insulin receptor substrates, IRS-1 and IRS-2 (refs 4,5,6,7,8), through distinct signalling pathways. Although a number of effectors of these pathways have been identified, their roles in mediating glucose homeostasis are poorly defined9. Here we show that mice deficient for S6 kinase 1, an effector of the phosphatidylinositide-3-OH kinase signalling pathway9, are hypoinsulinaemic and glucose intolerant. Whereas insulin resistance is not observed in isolated muscle, such mice exhibit a sharp reduction in glucose-induced insulin secretion and in pancreatic insulin content. This is not due to a lesion in glucose sensing or insulin production, but to a reduction in pancreatic endocrine mass, which is accounted for by a selective decrease in β-cell size. The observed phenotype closely parallels those of preclinical type 2 diabetes mellitus, in which malnutrition-induced hypoinsulinaemia predisposes individuals to glucose intolerance10,11,12.

Date: 2000
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/35050135 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:408:y:2000:i:6815:d:10.1038_35050135

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/35050135

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().