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Glucose regulates LXRα subcellular localization and function in rat pancreatic β-cells
作者姓名:Helleboid-Chapman A  Helleboid S  Jakel H  Timmerman C  Sergheraert C  Pattou F  Fruchart-Najib J  Fruchart JC
作者单位:Atherosclerosis Department UR 545 INSERM,the Faculty of Pharmacy,Lille 2 University,1 rue du Professeur Calmette BP245,Lille cedex 59019,France,Atherosclerosis Department,UR 545 INSERM,the Faculty of Pharmacy,Lille 2 University,1 rue du Professeur Calmette BP245,Lille cedex 59019,France,Atherosclerosis Department,UR 545 INSERM,the Faculty of Pharmacy,Lille 2 University,1 rue du Professeur Calmette BP245,Lille cedex 59019,France,Synthesis,Structure and Biomolecule Function,UMR 8525 CNRS,Pasteur Institute of Lille,Lille 2 University,Lille,France,Cell Therapy for Diabetes,ERIT-M 0106,Faculty,of Medecine University of Lille 2/INSERM,Lille 59045,France,Atherosclerosis Department,UR 545 INSERM,the Faculty of Pharmacy,Lille 2 University,1 rue du Professeur Calmette BP245,Lille cedex 59019,France,Atherosclerosis Department,UR 545 INSERM,the Faculty of Pharmacy,Lille 2 University,1 rue du Professeur Calmette BP245,Lille cedex 59019,France
基金项目:Acknowledgment This work was supported by research grants from Leducq foundation (02CVD02).
摘    要: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 LXRα protein level, but affects its localization in pancreatic β-cells. LXRα is found in the nucleus at 8 mM glucose and in the cytoplasm at 4.2 mM. Addition of glucose translocates LXRα 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 LXRα effect on insulin secretion, suggesting the involvement of glucose signaling through a phosphorylation-dependent mechanism.

关 键 词:LXRα  葡萄糖  亚细胞  胰腺β-细胞
收稿时间:2005-10-06
修稿时间:2005-10-062006-04-25

Glucose regulates LXRalpha subcellular localization and function in rat pancreatic beta-cells
Helleboid-Chapman A,Helleboid S,Jakel H,Timmerman C,Sergheraert C,Pattou F,Fruchart-Najib J,Fruchart JC.Glucose regulates LXRalpha subcellular localization and function in rat pancreatic beta-cells[J].Cell Research,2006,16(7):661-670.
Authors:Helleboid-Chapman Audrey  Helleboid Stéphane  Jakel Heidelinde  Timmerman Catherine  Sergheraert Christian  Pattou François  Fruchart-Najib Jamila  Fruchart Jean-Charles
Institution: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
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 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.
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