title: The nuclear receptor FXR is expressed in pancreatic beta-cells and protects human islets from lipotoxicity.
abstract: 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.
authors.affiliation: University Lille Nord de France, Lille, France.
authors.forename: Iuliana Ristea
authors.initials: IR
authors.lastname: Popescu
authors.forename: Audrey
authors.initials: A
authors.lastname: Helleboid-Chapman
authors.forename: Anthony
authors.initials: A
authors.lastname: Lucas
authors.forename: Brigitte
authors.initials: B
authors.lastname: Vandewalle
authors.forename: Julie
authors.initials: J
authors.lastname: Dumont
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Bouchaert
authors.forename: Bruno
authors.initials: B
authors.lastname: Derudas
authors.forename: Julie
authors.initials: J
authors.lastname: Kerr-Conte
authors.forename: Sandrine
authors.initials: S
authors.lastname: Caron
authors.forename: François
authors.initials: F
authors.lastname: Pattou
authors.forename: Bart
authors.initials: B
authors.lastname: Staels
mesh_terms: D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D066298:In Vitro Techniques; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D007555:Isoxazoles / Q000494:pharmacology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology*; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000819:agonists / Q000235:genetics / Q000378:metabolism* / Q000502:physiology*; D000099150:Receptor, Farnesoid X-Activated
chemical_list: D007555:Isoxazoles; D019308:Palmitic Acid; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C412815:GW 4064