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 |
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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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