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

被引：84
|
作者：
Popescu, Iuliana Ristea [1 ,2 ,3 ,4 ]
Helleboid-Chapman, Audrey [1 ,2 ,3 ,4 ]
Lucas, Anthony [1 ,2 ,3 ,4 ]
Vandewalle, Brigitte [2 ,4 ,5 ]
Dumont, Julie [1 ,2 ,3 ,4 ]
Bouchaert, Emmanuel [1 ,2 ,3 ,4 ]
Derudas, Bruno [1 ,2 ,3 ,4 ]
Kerr-Conte, Julie [2 ,4 ,5 ]
Caron, Sandrine [1 ,2 ,3 ,4 ]
Pattou, Francois [2 ,4 ,5 ]
Staels, Bart [1 ,2 ,3 ,4 ]
机构：
[1] Inst Pasteur, INSERM, UMR1011, F-59019 Lille, France
[2] Univ Lille Nord France, F-59000 Lille, France
[3] INSERM, UMR1011, F-59000 Lille, France
[4] UDSL, F-59000 Lille, France
[5] CHRU Lille, INSERM, U859, Lab Diabet Cell Therapy, F-59000 Lille, France
来源：
FEBS LETTERS | 2010年 / 584卷 / 13期
关键词：
Farnesoid X receptor; Type; 2; diabetes; Islet; Lipotoxicity; FARNESOID-X-RECEPTOR; BILE-ACIDS; INSULIN SENSITIVITY; GLUCOSE; GENE; ACTIVATION; SECRETION; LIGANDS; MICE;
D O I：
10.1016/j.febslet.2010.04.068
中图分类号：
Q5 [生物化学]; Q7 [分子生物学];
学科分类号：
071010 ; 081704 ;
摘要：
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 b-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. (C) 2010 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
引用
收藏
页码：2845 / 2851
页数：7
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