Effect of tumor necrosis factor-alpha on basal and insulin-stimulated glucose transport in cultured muscle and fat cells.
It has been reported that tumor necrosis factor-alpha (TNF-alpha) inhibits insulin action in adipocytes and plays an important role as mediator of insulin resistance in non-insulin-dependent diabetes. The effect of this cytokine on insulin action in muscle, which is responsible for 80% of the glucose disposal in the body, has not been studied. Therefore, we examined the effect of TNF-alpha on basal and insulin-mediated transport of 2-deoxy[3H]-glucose in L6 rat muscle cells. TNF-alpha treatment for 5 days up to a concentration of 20 ng/mL or 8 days at 10 ng/mL did not inhibit the insulin-stimulated increase in deoxyglucose transport in L6 cells. However, there was a significant increase in basal transport in TNF-alpha- treated cells. Comparative experiments with 3T3-L1 adipocytes showed that in cells cultured with insulin, TNF-alpha decreased basal transport but the insulin-stimulated increase was unaffected. In cells cultured without insulin, basal transport was slightly increased and the insulin-stimulated increase in transport was decreased by approximately 60% but the cell protein was decreased by approximately 60%, suggesting cytotoxicity. Cells cultured without insulin were more sensitive to inhibition of 14C-alanine incorporation into proteins by low concentrations of TNF-alpha compared with cells cultured with insulin. These results suggest that TNF-alpha affects glucose metabolism, causing increased basal uptake in muscle cells and decreased uptake in adipocytes. TNF-alpha appears to affect general cell metabolism, including glucose transport in adipocytes, and not specifically insulin-stimulated glucose transport.
Ranganathan
S
S
Research Institute, Cedars-Sinai Medical Center-UCLA, Los Angeles, CA, USA.
Davidson
M B
MB
D016475:3T3 Cells; D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002460:Cell Line; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D009132:Muscles / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D007328:Insulin; D014409:Tumor Necrosis Factor-alpha; D005947:Glucose