EFFECT OF TUMOR-NECROSIS-FACTOR-ALPHA ON BASAL AND INSULIN-STIMULATEDGLUCOSE-TRANSPORT IN CULTURED MUSCLE AND FAT-CELLS

It has been reported that tumor necrosis factor-alpha (TNF-alpha) inhi bits insulin action in adipocytes and plays an important role as media tor of insulin resistance in non-insulin-dependent diabetes. The effec t of this cytokine on insulin action in muscle, which is responsible f or 80% of the glucose disposal in the body, has not been studied. Ther efore, we examined the effect of TNF-alpha on basal and insulin-mediat ed transport of 2-deoxy[H-3]-glucose in L6 rat muscle cells. TNF-alpha treatment for 5 days up to a concentration of 20 ng/mL or 8 days at 1 0 ng/mL did not inhibit the insulin-stimulated increase in deoxyglucos e transport in L6 cells, However, there was a significant increase in basal transport in TNF-alpha-treated cells. Comparative experiments wi th 3T3-L1 adipocytes showed that in cells cultured with insulin, TNF-a lpha decreased basal transport but the insulin-stimulated increase was unaffected. In cells cultured without insulin, basal transport was sl ightly increased and the insulin-stimulated increase in transport was decreased by approximately 60% but the cell protein was decreased by a pproximately 60%, suggesting cytotoxicity. Cells cultured without insu lin were more sensitive to inhibition of C-14-alanine incorporation in to proteins by low concentrations of TNF-alpha compared with cells cul tured with insulin. These results suggest that TNF-alpha affects gluco se metabolism, causing increased basal uptake in muscle cells and decr eased uptake in adipocytes. TNF-alpha appears to affect general cell m etabolism, including glucose transport in adipocytes, and not specific ally insulin-stimulated glucose transport. Copyright (C) 1996 by W.B. Saunders Company