Regional Blood—Brain Glucose Transfer in the Rat: A Novel Double-Membrane Kinetic Analysis

Abstract

Regional blood–brain glucose transfer was studied in pentobarbitone-anaesthetized rats using a programmed intravenous infusion technique that maintained steady levels of unlabeled (up to 55 m M) and tracer d-glucose in the circulating plasma. Regional cerebral blood flow, glucose phosphorylation rate, and tissue glucose content were also measured under comparable conditions. Data were analysed in terms of irreversible Michaelis–Menten kinetics assuming independent influx and efflux (Type I) and reversible Michaelis–Menten kinetics (Type II) across both the luminal and the abluminal membranes of the endothelial cell. The latter analysis corresponds to simple stereospecific membrane pores. The mathematical model allowed for changes in tissue glucose content and back-diffusion of tracer during the experiments. Type I analyses gave Kt values of ∼6.6 m M, whereas those by Type II were consistently lower. Interregional differences were not significant using either scheme. Comparison of Type II with Type I analyses revealed a possible explanation for discrepancies in the estimates of nonsaturable glucose transfer by different methods and highlighted the importance of tissue glucose measurements in studies of unidirectional glucose influx. Since the experimental data may be described equally well by either scheme and some interaction between influx and efflux across the endothelial cell might be expected, consideration of this alternative approach is suggested.