Insulin and dexamethasone induce GLUT4 gene expression in foetal brown adipocytes: synergistic effect through CCAAT/enhancer-binding protein alpha
- 1 June 2003
- journal article
- Published by Portland Press Ltd. in Biochemical Journal
- Vol. 372 (2), 617-624
- https://doi.org/10.1042/bj20030325
Abstract
Treatment of foetal brown adipocytes in primary culture with either dexamethasone or insulin, at physiological concentrations, for 24 h up-regulates the expression of the GLUT4 gene, producing a synergistic effect on mRNA accumulation (20-fold increase), in the amount of protein in the total membrane fraction (8-fold increase) and in the transactivation of a full-promoter GLUT4-chloramphenicol acetyltransferase gene (CAT) construct (7-fold increase). However, GLUT1 expression remains essentially unmodified regardless of the presence of the hormones. As a consequence, exposure of brown adipocytes to dexamethasone and insulin results in a dramatic increase of glucose uptake (12-fold). Dexamethasone induces the expression of CCAAT/enhancer-binding protein (C/EBP) α, insulin promotes myocyte enhancer factor-2 DNA-binding activity and both combined produces a significant increase in C/EBPα DNA-binding activity. Moreover, co-transfection with a wild-type C/EBPα construct transactivates a full-promoter GLUT4-CAT fusion gene, whereas a dominant-negative C/EBPα expression vector impairs the hormonal effects. Our results show that the synergism between insulin and glucocorticoids on glucose uptake is a consequence of the activation of the GLUT4 promoter by the transcription factor C/EBPα.Keywords
This publication has 37 references indexed in Scilit:
- PPARα Activation by Wy 14643 Induces Transactivation of the Rat UCP-1 Promoter without Increasing UCP-1 mRNA Levels and Attenuates PPARγ-Mediated Increases in UCP-1 mRNA Levels Induced by Rosiglitazone in Fetal Rat Brown AdipocytesBiochemical and Biophysical Research Communications, 1999
- Dependence of Insulin-Stimulated Glucose Transporter 4 Translocation on 3-Phosphoinositide-Dependent Protein Kinase-1 and Its Target Threonine-410 in the Activation Loop of Protein Kinase C-ζMolecular Endocrinology, 1999
- Identification of a Novel Enhancer Sequence in the Distal Promoter of the Rat Fatty Acid Synthase GeneBiochemical and Biophysical Research Communications, 1999
- An Inhibitor of p38 Mitogen-activated Protein Kinase Prevents Insulin-stimulated Glucose Transport but Not Glucose Transporter Translocation in 3T3-L1 Adipocytes and L6 MyotubesPublished by Elsevier ,1999
- The Transcription Factor Nuclear Factor I Mediates Repression of the GLUT4 Promoter by InsulinPublished by Elsevier ,1999
- Reconstitution of Insulin-sensitive Glucose Transport in Fibroblasts Requires Expression of Both PPARγ and C/EBPαJournal of Biological Chemistry, 1999
- Insulin and insulin-like growth factor I up-regulate GLUT4 gene expression in fetal brown adipocytes, in a phosphoinositide 3-kinase-dependent manner.1999
- GLUT4Gene Regulation and ManipulationJournal of Biological Chemistry, 1999
- Myocyte Enhancer Factor 2 (MEF2)-Binding Site Is Required forGLUT4 Gene Expression in Transgenic MicePublished by Elsevier ,1998
- Construction and Characterization of a Conditionally Active Version of the Serine/Threonine Kinase AktJournal of Biological Chemistry, 1998