Hepatic glucose sensing is required to preserve β cell glucose competence.

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Etat: Public
Version: de l'auteur
ID Serval
serval:BIB_FD22C2D96632
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Hepatic glucose sensing is required to preserve β cell glucose competence.
Périodique
Journal of Clinical Investigation
Auteur(s)
Seyer P., Vallois D., Poitry-Yamate C., Schütz F., Metref S., Tarussio D., Maechler P., Staels B., Lanz B., Grueter R., Decaris J., Turner S., da Costa A., Preitner F., Minehira K., Foretz M., Thorens B.
ISSN
1558-8238 (Electronic)
ISSN-L
0021-9738
Statut éditorial
Publié
Date de publication
2013
Volume
123
Numéro
4
Pages
1662-1676
Langue
anglais
Résumé
Liver glucose metabolism plays a central role in glucose homeostasis and may also regulate feeding and energy expenditure. Here we assessed the impact of glucose transporter 2 (Glut2) gene inactivation in adult mouse liver (LG2KO mice). Loss of Glut2 suppressed hepatic glucose uptake but not glucose output. In the fasted state, expression of carbohydrate-responsive element-binding protein (ChREBP) and its glycolytic and lipogenic target genes was abnormally elevated. Feeding, energy expenditure, and insulin sensitivity were identical in LG2KO and control mice. Glucose tolerance was initially normal after Glut2 inactivation, but LG2KO mice exhibited progressive impairment of glucose-stimulated insulin secretion even though β cell mass and insulin content remained normal. Liver transcript profiling revealed a coordinated downregulation of cholesterol biosynthesis genes in LG2KO mice that was associated with reduced hepatic cholesterol in fasted mice and reduced bile acids (BAs) in feces, with a similar trend in plasma. We showed that chronic BAs or farnesoid X receptor (FXR) agonist treatment of primary islets increases glucose-stimulated insulin secretion, an effect not seen in islets from Fxr-/- mice. Collectively, our data show that glucose sensing by the liver controls β cell glucose competence and suggest BAs as a potential mechanistic link.
Pubmed
Web of science
Open Access
Oui
Création de la notice
29/04/2013 9:41
Dernière modification de la notice
20/08/2019 16:28
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