| First Author | Long SD | Year | 1996 |
| Journal | Biochem J | Volume | 319 ( Pt 1) |
| Pages | 179-84 | PubMed ID | 8870666 |
| Mgi Jnum | J:35889 | Mgi Id | MGI:83332 |
| Doi | 10.1042/bj3190179 | Citation | Long SD, et al. (1996) Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4 gene transcription in 3T3-L1 adipocytes. Biochem J 319(Pt 1):179-84 |
| abstractText | We have previously demonstrated that chronic exposure of 3T3-L1 adipocytes to tumour necrosis factor-alpha (TNF) resulted in a marked decrease (approximately 90%) in cellular GLUT4 (insulin-responsive glucose transporter) mRNA content as a result of a decreased transcription rate of the GLUT4 gene (approximately 75%) and a reduced half-life of its mRNA (9 to 4.5 h). Investigation of the signalling mechanism responsible for this regulation demonstrated that in the 3T3-L1 adipocytes, sphingomyelin levels decreased to 50% of control levels within 40 min of exposure to TNF, consistent with activation of a sphingomyelinase. In the same manner as with TNF, treatment of the adipocytes with 1-3 microM C6-ceramide, a membrane-permeable analogue of ceramide, decreased GLUT4 mRNA content by approximately 60%. Subsequent investigations revealed that transcription of the GLUT4 gene was reduced by approximately 65% in response to C6-ceramide, demonstrating that the decrease in mRNA content is mediated by a reduction in the transcription of the genc. No effect on GLUT4 mRNA stability was observed after exposure of the adipocytes to C6-ceramide. These observations are interesting in light of our previous data demonstrating that TNF affects both GLUT4 transcription and mRNA stability in the 3T3-L1 adipocytes. In conclusion, the effect of ceramide on GLUT4 gene expression is at the level of transcription, suggesting that another pathway controls mRNA stability. These data establish that ceramide-initiated signal transduction pathways exist within the adipocyte, and provide a potential mechanism for control of GLUT4 gene expression. |
