The present studies were undertaken to assess the mechanism by which insulin increases glucose uptake in man. Because glucose uptake in most mammalian tissues occurs predominantly by a facilitated transport system that follows Michaelis-Menten kinetics, glucose uptake was measured isotopically in normal volunteers over the physiologic range of plasma glucose and insulin concentrations and was subjected to Lineweaver-Burk and Eadie-Hofstee analysis. With both methods, increases in plasma insulin from 18 μU/ml to 80 and 150 μU/ml were found to increase the maximum velocity (V(max)) for glucose uptake nearly 3- and 5-fold, respectively (P < 0.025 and P < 0.001), without significantly altering the Michaelis constant (K(m)). Because an increase in the affinity or molecular activity of transport sites or provision of additional transport sites that differed from those present basally should have altered the K(m), whereas a mere increase in the number of transport sites would have only increased the V(max), our results indicate that in man, insulin may increase glucose uptake merely by providing additional transport sites.
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