Glucose regulates LXRalpha subcellular localization and function in rat pancreatic beta-cells.
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 LXRalpha protein level, but affects its localization in pancreatic beta-cells. LXRalpha is found in the nucleus at 8 mM glucose and in the cytoplasm at 4.2 mM. Addition of glucose translocates LXRalpha 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 LXRalpha effect on insulin secretion, suggesting the involvement of glucose signaling through a phosphorylation-dependent mechanism.
Helleboid-Chapman
Audrey
A
Atherosclerosis Department, UR 545 INSERM, the Faculty of Pharmacy, Lille 2 University, 1 rue du Professeur Calmette BP245, Lille cedex 59019, France. audrey.chapman@pasteur-lille.fr
Helleboid
Stéphane
S
Jakel
Heidelinde
H
Timmerman
Catherine
C
Sergheraert
Christian
C
Pattou
François
F
Fruchart-Najib
Jamila
J
Fruchart
Jean-Charles
JC
D000818:Animals; D002478:Cells, Cultured; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006845:Hydrocarbons, Fluorinated; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D000071518:Liver X Receptors; D019319:Okadaic Acid / Q000378:metabolism; D057093:Orphan Nuclear Receptors; D010455:Peptides / Q000235:genetics / Q000378:metabolism; D051381:Rats; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics / Q000378:metabolism*; D051780:Sterol Regulatory Element Binding Protein 1 / Q000378:metabolism; D013449:Sulfonamides / Q000378:metabolism; D019014:fas Receptor / Q000378:metabolism; D005466:Fluorocarbons; D000096926:Benzenesulfonamides
D004268:DNA-Binding Proteins; D004791:Enzyme Inhibitors; D005947:Glucose; D006845:Hydrocarbons, Fluorinated; D007328:Insulin; D000071518:Liver X Receptors; D019319:Okadaic Acid; D057093:Orphan Nuclear Receptors; D010455:Peptides; D018160:Receptors, Cytoplasmic and Nuclear; D051780:Sterol Regulatory Element Binding Protein 1; D013449:Sulfonamides; D019014:fas Receptor; C000605215:Nr1h3 protein, rat; C423915:T0901317; D005466:Fluorocarbons; D000096926:Benzenesulfonamides