We examined the effects of acute administration of tolbutamide on glucose uptake in the non-cyclically perfused rat hindlimb. During the hour of study, 500 microunits boluses of insulin were given every ten min in the presence or absence of 3 X 10(-3)M tolbutamide. Tolbutamide by itself increased glucose uptake; however at no time was this increase significantly different from that seen in the group which received insulin alone. After 42 min of perfusion, the insulin-stimulated uptake was 26% and the tolbutamide was 20% greater than control (1.90 +/- 0.08, 1.80 +/- 0.06, and 1.50 +/- 0.05 mumol/min/100 g respectively). After 20 min of perfusion, the increase in glucose uptake seen with the combination of insulin + tolbutamide was significantly greater than that obtained with either tolbutamide or insulin alone. At the termination of perfusion, the glucose uptake with the combined treatment was 59% greater than control, 35% greater than tolbutamide, and 19% greater than insulin alone (2.67 +/- 0.10, vrs. 1.68 +/- 0.07 vrs. 1.97 +/- 0.07 vrs. 2.16 +/- 0.07 mumol/min/100 g). These results demonstrate not only a direct effect of tolbutamide, but also a potentiation of insulin-stimulated glucose uptake in the rat hindlimb. Therefore, tolbutamide has extra-pancreatic effects which probably contribute to the hypoglycemic action of this sulfonylurea.
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