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The nuclear receptor FXR is expressed in pancreatic β‐cells and protects human islets from lipotoxicity
Author(s) -
Popescu Iuliana Ristea,
Helleboid-Chapman Audrey,
Lucas Anthony,
Vandewalle Brigitte,
Dumont Julie,
Bouchaert Emmanuel,
Derudas Bruno,
Kerr-Conte Julie,
Caron Sandrine,
Pattou François,
Staels Bart
Publication year - 2010
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2010.04.068
Subject(s) - farnesoid x receptor , lipotoxicity , medicine , islet , endocrinology , nuclear receptor , glucose homeostasis , beta cell , biology , pancreatic islets , cytosol , microbiology and biotechnology , chemistry , insulin , transcription factor , gene , insulin resistance , biochemistry , enzyme
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 β‐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 β‐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.