JOURNAL ARTICLE

Transcriptional repression of the GLUT4 and C/EBP genes in 3T3-L1 adipocytes by tumor necrosis factor-alpha

J M Stephens, P H Pekala
Journal of Biological Chemistry 1991 November 15, 266 (32): 21839-45
1939208
Fully differentiated 3T3-L1 adipocytes were chronically exposed to 5 nM tumor necrosis factor-alpha (TNF). This resulted in the development of an insulin resistance based on the inability of insulin to stimulate hexose uptake. Western blot analysis for glucose transporter protein in isolated membrane fractions indicated a total depletion of GLUT4 protein (insulin-responsive glucose transporter) in cells chronically treated with TNF. Plasma membrane content of GLUT1 protein (growth-related glucose transporter) was similar in both control and TNF-treated cells; however, the GLUT1 content of the intracellular membrane compartment had decreased markedly after TNF treatment. Continuous exposure to TNF resulted in an 85-90% decrease in the mRNA content for both GLUT4 and 422 (aP2, a lipid binding protein) genes relative to age matched controls, whereas insulin receptor mRNA levels declined by at least 50%. This was preceded by a marked decrease in mRNA accumulation for C/EBP, a transcription factor proposed to control expression of both GLUT4 and 422. The specificity of these observations was demonstrated by the lack of an effect of the chronic TNF treatment on either beta-actin or lipoprotein lipase mRNA content. The decreased content of GLUT4 and C/EBP mRNA was judged to be regulated at least in part at the level of transcription, based on the results of transcription run-on assays. Thus, the lack of response to insulin appeared due to a suppression of GLUT4 expression as well as a decreased intracellular content of GLUT1.

Full Text Links

Find Full Text Links for this Article

Discussion

You are not logged in. Sign Up or Log In to join the discussion.

Trending Papers

Remove bar
Read by QxMD icon Read
1939208
×

Save your favorite articles in one place with a free QxMD account.

×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"