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

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    Author
    Long, Sheree D.; Pekala, Phillip H.
    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
    URI
    http://hdl.handle.net/10342/3338
    Subject
     Insulin resistance; Glut4; Adipocytes 
    Date
    1996-10-01
    Citation:
    APA:
    Long, Sheree D., & Pekala, Phillip H.. (October 1996). Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4 gene transcription in 3T3-L1 adipocytes.. Biochemical Journal, 319(1), 179- 184. Retrieved from http://hdl.handle.net/10342/3338

    Display/Hide MLA, Chicago and APA citation formats.

    MLA:
    Long, Sheree D., and Pekala, Phillip H.. "Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4 gene transcription in 3T3-L1 adipocytes.". Biochemical Journal. 319:1. (179-184), October 1996. September 30, 2023. http://hdl.handle.net/10342/3338.
    Chicago:
    Long, Sheree D. and Pekala, Phillip H., "Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4 gene transcription in 3T3-L1 adipocytes.," Biochemical Journal 319, no. 1 (October 1996), http://hdl.handle.net/10342/3338 (accessed September 30, 2023).
    AMA:
    Long, Sheree D., Pekala, Phillip H.. Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4 gene transcription in 3T3-L1 adipocytes.. Biochemical Journal. October 1996; 319(1): 179-184. http://hdl.handle.net/10342/3338. Accessed September 30, 2023.
    Collections
    • Biochemistry and Molecular Biology
    Publisher
    East Carolina University

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