title: Acute tolbutamide administration alone or combined with insulin enhances glucose uptake in the perfused rat hindlimb.
abstract: 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.
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006614:Hindlimb; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D010477:Perfusion; D051381:Rats; D011919:Rats, Inbred Strains; D014044:Tolbutamide / Q000494:pharmacology*
chemical_list: D007328:Insulin; D014044:Tolbutamide; D005947:Glucose