title: Glucose utilization in rat adipocytes. The interaction of transport and metabolism as affected by insulin.
abstract: 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.
mesh_terms: D019325:3-O-Methylglucose; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D003201:Computers; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
chemical_list: D005958:Glucosephosphates; D007328:Insulin; D008757:Methylglucosides; D019325:3-O-Methylglucose; D019298:Glucose-6-Phosphate; D005947:Glucose