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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.. , (. Retrieved from http://hdl.handle.net/10342/3338

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    MLA:
    Long, Sheree D., and Pekala, Phillip H.. "Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4 gene transcription in 3T3-L1 adipocytes.". . . (.), October 1996. February 24, 2021. 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.,"  , no. (October 1996), http://hdl.handle.net/10342/3338 (accessed February 24, 2021).
    AMA:
    Long, Sheree D., Pekala, Phillip H.. Lipid mediators of insulin resistance: ceramide signalling down-regulates GLUT4 gene transcription in 3T3-L1 adipocytes.. . October 1996; () . http://hdl.handle.net/10342/3338. Accessed February 24, 2021.
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    • Biochemistry and Molecular Biology
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    East Carolina University

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