1. ¹Atherosclerosis Department, UR 545 INSERM, the Faculty of Pharmacy, Lille 2 University, 1 rue du Professeur Calmette BP245, Lille cedex 59019, France
2. ²Synthesis, Structure and Biomolecule Function, UMR 8525 CNRS, Pasteur Institute of Lille, Lille 2 University, Lille, France
3. ³Cell Therapy for Diabetes, ERIT-M 0106, Faculty of Medecine University of Lille 2/INSERM, Lille 59045, France

Correspondence: Audrey Helleboid-Chapman, Tel: +33-3-20-87-78-74; Fax: +33-3-20-87-73-60; E-mail: audrey.chapman@pasteur-lille.fr

Received 6 October 2005; Revised 20 March 2006; Accepted 25 April 2006; Published online   .

Abstract

Liver X receptors (LXRs) are members of the nuclear receptor superfamily, which have been implicated in lipid homeostasis and more recently in glucose metabolism. Here, we show that glucose does not change LXR protein level, but affects its localization in pancreatic -cells. LXR is found in the nucleus at 8 mM glucose and in the cytoplasm at 4.2 mM. Addition of glucose translocates LXR from the cytoplasm into the nucleus. Moreover, after the activation of LXR by its synthetic non-steroidal agonist (T0901317), insulin secretion and glucose uptake are increased at 8 mM and decreased at 4.2 mM glucose in a dose-dependent manner. Furthermore, at low glucose condition, okadaic acid reversed LXR effect on insulin secretion, suggesting the involvement of glucose signaling through a phosphorylation-dependent mechanism.