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.
Popescu
Iuliana Ristea
IR
University Lille Nord de France, Lille, France.
Helleboid-Chapman
Audrey
A
Lucas
Anthony
A
Vandewalle
Brigitte
B
Dumont
Julie
J
Bouchaert
Emmanuel
E
Derudas
Bruno
B
Kerr-Conte
Julie
J
Caron
Sandrine
S
Pattou
François
F
Staels
Bart
B
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
D007555:Isoxazoles; D019308:Palmitic Acid; D018160:Receptors, Cytoplasmic and Nuclear; D000099150:Receptor, Farnesoid X-Activated; C412815:GW 4064