Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4 gene transcription in 3T3-L1 adipocytes.

ECU Author/Contributor (non-ECU co-authors, if there are any, appear on document)

Sheree D. Long (Creator)

Phillip H. Pekala (Creator)

Institution

East Carolina University (ECU )

Web Site: http://www.ecu.edu/lib/

Abstract: We have previously demonstrated that chronic exposure of 3T3- L1 adipocytes to tumour necrosis factor-α (TNF) resulted in a marked decrease (~90%) in cellular GLUT4 (insulin-responsive glucose transporter) mRNA content as a result of a decreased transcription rate of the GLUT4 gene (~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 μMC6-ceramide a membrane-permeable analogue of ceramide decreased GLUT4 mRNA content by 60%. Subsequent investigations revealed that transcription of the GLUT4 gene was reduced by~65% in response to C6-ceramide demonstrating that the decrease in mRNA content is mediated by a reduction in the transcription of the gene. 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 andmRNA 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 controlsmRNA 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. Originally published Biochemical Journal Vol. 319 No. 1 Oct 1996

Additional Information

Publication

Other

Biochemical Journal. 319:1(October 1996) p. 179-184.

Language: English

Date: 2011

Keywords

Insulin resistance, Glut4, adipocytes

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