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

Autor: François Pattou, Iuliana Popescu, Julie Kerr-Conte, Anthony Lucas, Sandrine Caron, Emmanuel Bouchaert, Audrey Helleboid-Chapman, Bart Staels, Julie Dumont, Bruno Derudas, Brigitte Vandewalle
Přispěvatelé: Récepteurs nucléaires, maladies cardiovasculaires et diabète - U 1011 (RNMCD), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Thérapie cellulaire du diabète, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille, Droit et Santé, Derudas, Marie-Hélène
Jazyk: angličtina
Rok vydání: 2010
Předmět:
Male
Palmitic Acid
Receptors
Cytoplasmic and Nuclear
Biochemistry
Mice
0302 clinical medicine
Structural Biology
Insulin-Secreting Cells
Glucose homeostasis
Receptor
Cells
Cultured
islets
0303 health sciences
Bile acid
lipotoxicity
Lipotoxicity
FXR
Small heterodimer partner
type 2 diabetes
Islet
medicine.medical_specialty
endocrine system
medicine.drug_class
Blotting
Western
Biophysics
030209 endocrinology & metabolism
In Vitro Techniques
Biology
Islets of Langerhans
03 medical and health sciences
Farnesoid X receptor
Internal medicine
[SDV.BBM] Life Sciences [q-bio]/Biochemistry
Molecular Biology
Genetics
medicine
Animals
Humans
[SDV.BBM]Life Sciences [q-bio]/Biochemistry
Molecular Biology
Obesity
Liver X receptor
Molecular Biology
030304 developmental biology
Isoxazoles
Cell Biology
Mice
Mutant Strains
Rats
Mice
Inbred C57BL
Endocrinology
Nuclear receptor
Zdroj: FEBS Letters
FEBS Letters, 2010, 584 (13), pp.2845-51. ⟨10.1016/j.febslet.2010.04.068⟩
FEBS Letters, Wiley, 2010, 584 (13), pp.2845-51. ⟨10.1016/j.febslet.2010.04.068⟩
ISSN: 0014-5793
1873-3468
Popis: International audience; 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.
Databáze: OpenAIRE
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