Kinetics of Regional Blood–Brain Barrier Transport and Brain Phosphorylation of Glucose and 2‐Deoxyglucose in the Barbiturate–Anesthetized Rat

Abstract

Recent studies indicate the lumped constant (LC), which defines the relative rates of brain utilization of glucose and 2-deoxyglucose (2-DG), doubles to values greater than 1.0 under conditions of hypoglycemia. Since changes in the LC should be predictable given the kinetic parameters of blood-brain barrier (BBB) transport and brain phosphorylation of glucose and 2-DG, the present studies were designed to measure the necessary kinetic parameters. The carotid injection technique ws used to determine cerebral blood flow and the Km, Vmax, and KD of glucose and 2-DG transport through the BBB in seven brain regions in rats anesthetized with 50 mg/kg i.lp. pentobarbital. Regional glucose transport through the BBB was characterized by an average Km = 6.3 mM, average Vmax = 0.53 mumol min-1g-1, and average KD = 0.022 ml min-1g-1.l The nonsaturable route of transport of glucose represented on the average 40% of the total glucose influx into brain regions at an arterial glucose concentration of 10 mM. In addition, the rate constants of phosphorylation of glucose and 2-DG were measured for each region. Substitutions of the measured kinetic parameters for sugar transport and phosphorylation into equations defining the LC confirm the observation that the LC would be expected to vary under extreme conditions such as hypoglycemia and to exceed values of 1.0 under these conditions.