Estimation and kinetic analysis of insulin-independent glucose uptake in human subjects

Using the glucose clamp technique, glucose uptake was determined isotopically in normal human volunteers at plasma glucose concentrations of ≃60, 95, and 160 mg/dl during insulin infusions that increased plasma insulin to ≃20, 80, and 160 μU/ml. Because glucose uptake was found to be a linear function of plasma insulin at each plasma glucose concentration (r > 0.92, P < 0.01), glucose uptake at 0 plasma insulin was estimated by linear regression analysis. The values thus derived (1.30, 1.62, and 2.59 mg · kg^-1 · min^-1 for plasma glucose concentrations of 60, 95, and 160 mg/dl, respectively) produced a linear Eadie-Hofstee plot, suggesting that insulin-independent glucose uptake followed Michaelis-Menten kinetics. The K(m) for glucose uptake at 0 plasma insulin (≃10 mM) was similar to those observed for glucose uptake at the other plasma insulin concentrations studied (≃9-12 mM), but its V(max) was less (5.2 vs. 6.4, 18.5, and 26.8 mg · kg^-1 · min^-1 for ≃20, 80, and 160 U/ml, respectively). These results indicate that in postabsorptive human subjects 75-85% of glucose uptake is noninsulin-mediated and provide additional support for the concept that insulin may increase glucose uptake merely by providing additional transport sites. The method described herein provides an assessment of insulin-dependent glucose uptake in vivo that may prove useful in distinguishing between intrinsic defects of the glucose transport system and those due to defects in insulin action.