EFFECTS OF TUMOR-NECROSIS-FACTOR-ALPHA ON GLUCOSE-METABOLISM IN CULTURED HUMAN MUSCLE-CELLS FROM NONDIABETIC AND TYPE-2 DIABETIC SUBJECTS

The effects of tumor necrosis factor-alpha (TNF alpha) on glucose upta ke and glycogen synthase (GS) activity were studied in human skeletal muscle cell cultures from nondiabetic and type 2 diabetic subjects. In nondiabetic muscle cells, acute (90-min) exposure to TNF alpha (5 ng/ ml) stimulated glucose uptake (73 +/- 14% increase) to a greater exten t than insulin (37 +/- 4%; P < 0.02). The acute uptake response to TNF a in diabetic cells (51 +/- 6% increase) was also greater than that to insulin (31 +/- 3%; P < 0.05). Prolonged (24-h) exposure of nondiabet ic muscle cells to TNF alpha resulted in a further stimulation of upta ke (152 +/- 31%; P < 0.05), whereas the increase in cells from type 2 diabetics was not significant compared with that in cells receiving ac ute treatment. After TNF alpha treatment, the level of glucose transpo rter-1 protein was elevated in nondiabetic (4.6-fold increase) and typ e 2 (1.7-fold) cells. Acute TNF alpha treatment had no effect on the f ractional velocity of GS in either nondiabetic or type 2 cells. Prolon ged exposure reduced the GS fractional velocity in both nondiabetic an d diabetic cells. In summary, both acute and prolonged treatment with TNF alpha up-regulate glucose uptake activity in cultured human muscle cells, but reduce GS activity. Increased skeletal muscle glucose upta ke in conditions of TNF alpha excess may serve as a compensatory mecha nism in the insulin resistance of type 2 diabetes.