Glucose utilization in rat adipocytes. The interaction of transport and metabolism as affected by insulin

The relative contributions of transport and intracellular metabolism of glucose to the control of overall glucose utilization were evaluated in rat adipocytes. Transport of 3-O-methylglucose and hexokinase activity in crude homogenates were measured and the derived kinetic parameters incorporated into network thermodynamic computer simulations. Hexokinase was found to be inhibited in a fully noncompetitive pattern by glucose 6-phosphate (Ki = 0.46 mM). When this feature was incorporated into the computer simulations, they reflected measured rates of overall glucose utilization as well as intracellular glucose 6-phosphate concentrations, both in the presence and absence of insulin. The effect of the hormone was represented in the simulations solely by an increase in the number of hexose carriers. A predominant stimulation of transport rather than metabolism was also suggested by the finding that intracellular glucose concentrations assessed by glucose-induced 3-O-methylglucose counter-transport were higher in the presence than in the absence of insulin over a wide range of extracellular glucose concentrations. Nevertheless, it was also found that insulin induced a significant countertransport gradient while the oxidant H2O2 did not, which suggests that insulin-stimulated metabolism does increase overall glucose utilization independently of effects on transport. These studies show that the kinetic patterns of basal and insulin-stimulated glucose utilization in adipocytes may be generated simply by coupling transport and phosphorylation steps and providing for inhibition of the latter by accumulated glucose 6-phosphate.