To investigate the role of skeletal muscle tissue expression of the glucose transporter protein GLUT1 in mediating glucose disposal in the basal (fasting) state, skeletal muscle biopsies (vastus lateralis) were obtained from lean and obese nondiabetics and type 2 diabetic subjects. Basal and insulin-stimulated glucose uptakes were measured. Basal whole body glucose uptake was measured using isotope dilution, and arteriovenous catheterization limb balance was used to determine leg muscle glucose uptake. Basal (noninsulin-stimulated) whole body glucose uptake was higher in the type 2 group compared with the controls (2.26 +/- 0.17 vs. 1.83 +/- 0.15 mg/kg.min; P < 0.05). However, basal leg muscle glucose uptake was reduced in diabetic subjects (1.53 +/- 0.56 vs. 3.89 +/- 0.83 mg/100 ml.min; P < 0.025) despite basal hyperglycemia (230 +/- 13 vs. 94 +/- 2 mg/dl; P < 0.0005). Skeletal muscle GLUT1 protein expression was lower in the type 2 subjects (57 +/- 12 vs. 91 +/- 11 arbitrary units/10 microg protein; P < 0.05), although GLUT1 mRNA levels did not differ. In summary, 1) skeletal muscle tissue GLUT1 protein expression is reduced in type 2 diabetes and could contribute to impaired basal leg glucose uptake; and 2) elevated rates of basal whole body glucose uptake in type 2 diabetes are due to uptake in tissues other than skeletal muscle.