The nuclear receptor FXR is expressed in pancreatic beta-cells and protects human islets from lipotoxicity.

Farnesoid X receptor (FXR) is highly expressed in liver and intestine where it controls bile acid (BA), lipid and glucose homeostasis. Here we show that FXR is expressed and functional, as assessed by target gene expression analysis, in human islets and beta-cell lines. FXR is predominantly cytosolic-localized in the islets of lean mice, but nuclear in obese mice. Compared to FXR+/+ mice, FXR-/- mice display a normal architecture and beta-cell mass but the expression of certain islet-specific genes is altered. Moreover, glucose-stimulated insulin secretion (GSIS) is impaired in the islets of FXR-/- mice. Finally, FXR activation protects human islets from lipotoxicity and ameliorates their secretory index.

Mots clés

FXR type 2 diabetes islets lipotoxicity

Domaines

Biochimie, Biologie Moléculaire

Fichier principal

Art_RISTEA.pdf (522.72 Ko)

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Marie-Hélène Derudas : Connectez-vous pour contacter le contributeur

https://inserm.hal.science/inserm-00485665

Soumis le : vendredi 21 mai 2010-14:14:47

Dernière modification le : vendredi 19 avril 2024-14:04:05

Archivage à long terme le : jeudi 1 décembre 2016-00:13:34

Dates et versions

inserm-00485665 , version 1 (21-05-2010)

Identifiants

HAL Id : inserm-00485665 , version 1
DOI : 10.1016/j.febslet.2010.04.068
PUBMED : 20447400

Citer

Iuliana Ristea Popescu, Audrey Helleboid-Chapman, Anthony Lucas, Brigitte Vandewalle, Julie Dumont, et al.. The nuclear receptor FXR is expressed in pancreatic beta-cells and protects human islets from lipotoxicity.. FEBS Letters, 2010, 584 (13), pp.2845-51. ⟨10.1016/j.febslet.2010.04.068⟩. ⟨inserm-00485665⟩

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