Titre
Hypoinsulinaemia, glucose intolerance and diminished beta-cell size in S6K1-deficient mice.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Pende, M.
Auteure/Auteur
Kozma, S.C.
Auteure/Auteur
Jaquet, M.
Auteure/Auteur
Oorschot, V.
Auteure/Auteur
Burcelin, R.
Auteure/Auteur
Le Marchand-Brustel, Y.
Auteure/Auteur
Klumperman, J.
Auteure/Auteur
Thorens, B.
Auteure/Auteur
Thomas, G.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
0028-0836
Statut éditorial
Publié
Date de publication
2001-12
Volume
408
Numéro
6815
Première page
994
Dernière page/numéro d’article
997
Peer-reviewed
Oui
Langue
anglais
Résumé
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. Here we show that mice deficient for S6 kinase 1, an effector of the phosphatidylinositide-3-OH kinase signalling pathway, 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 beta-cell size. The observed phenotype closely parallels those of preclinical type 2 diabetes mellitus, in which malnutrition-induced hypoinsulinaemia predisposes individuals to glucose intolerance.
PID Serval
serval:BIB_B9D4B88893AF
PMID
Date de création
2008-01-24T12:41:42.875Z
Date de création dans IRIS
2025-05-21T03:51:40Z