Arachidonic acid down-regulates the insulin-dependent glucose transporter gene (GLUT4) in 3T3-L1 adipocytes by inhibiting transcription and enhancing mRNA turnover
Chronic exposure of fully differentiated 3T3-L1 adipocytes to 50 μM arachidonic acid (AA) resulted in an inhibition (~91%) in cellular GLUT4 mRNA content after a 48-h exposure, without similarly affecting the mRNA content of the ubiquitous glucose transporter, GLUT1. Subsequent investigations revealed that transcription of the GLUT4 gene was reduced by ~50% in response to AA treatment and the half-life of GLUT4 mRNA decreased from 8.0 to 4.6 h. By contrast, AA increased the accumulation of GLUT1 mRNA by 65%, by a mechanism that also involved regulation at both transcriptional and mRNA stability levels. Western blot analysis revealed that AA was specifically reducing the insulin-responsive glucose transporter (GLUT4) in both plasma and intracellular membranes. Subsequently, AA was observed to alter the ability of the GLUT4 transporter to respond to insulin and mediate a significant enhancement of glucose uptake. The results presented in this study indicate that AA can partially mimic the effects of both tumor necrosis factor-α and insulin which, when chronically supplied to 3T3-L1 adipocytes, also down-regulate GLUT4 gene expression. Therefore, these data may have relevance to the insulin-resistance associated with non-insulin-dependent diabetes mellitus.
Publication Source (Journal or Book title)
Journal of Biological Chemistry
Tebbey, P., McGowan, K., Stephens, J., Buttke, T., & Pekala, P. (1994). Arachidonic acid down-regulates the insulin-dependent glucose transporter gene (GLUT4) in 3T3-L1 adipocytes by inhibiting transcription and enhancing mRNA turnover. Journal of Biological Chemistry, 269 (1), 639-644. Retrieved from https://digitalcommons.lsu.edu/biosci_pubs/3334