STEADY-STATE CEREBRAL GLUCOSE-CONCENTRATIONS AND TRANSPORT IN THE HUMAN BRAIN

Understanding the mechanism of brain glucose transport across the bloo d-brain barrier is of importance to understanding brain energy metabol ism. The specific kinetics of glucose transport have been generally de scribed using standard Michaelis-Menten kinetics. These models predict that the steady-state glucose concentration approaches an upper limit in the human brain when the plasma glucose level is well above the Mi chaelis-Menten constant for half-maximal transport, K-t. In experiment s where steady-state plasma glucose content was varied from 4 to 30 mM , the brain glucose level was a linear function of plasma glucose conc entration. At plasma concentrations nearing 30 mM, the brain glucose l evel approached 9 mM, which was significantly higher than predicted fr om the previously reported K-t of similar to 4 mM (p < 0.05). The high brain glucose concentration measured in the human brain suggests that ablumenal brain glucose may compete with lumenal glucose for transpor t. We developed a model based on a reversible Michaelis-Menten kinetic formulation of unidirectional transport rates. Fitting this model to brain glucose level as a function of plasma glucose level gave a subst antially lower K-t of 0.6 +/- 2.0 mM, which was consistent with the pr eviously reported millimolar K-m of GLUT-1 in erythrocyte model system s. Previously reported and reanalyzed quantification provided consiste nt kinetic parameters. We conclude that cerebral glucose transport is most consistently described when using reversible Michaelis-Menten kin etics.