Steady‐State Cerebral Glucose Concentrations and Transport in the Human Brain

Abstract

Abstract: Understanding the mechanism of brain glucose transport across the blood‐brain barrier is of importance to understanding brain energy metabolism. The specific kinetics of glucose transport have been generally described 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 Michaelis‐Menten constant for half‐maximal transport, Kt. In experiments where steady‐state plasma glucose content was varied from 4 to 30 m M, the brain glucose level was a linear function of plasma glucose concentration. At plasma concentrations nearing 30 m M, the brain glucose level approached 9 m M, which was significantly higher than predicted from the previously reported Kt of ∼4 m M (p < 0.05). The high brain glucose concentration measured in the human brain suggests that ablumenal brain glucose may compete with lumenal glucose for transport. 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 substantially lower Kt of 0.6 ± 2.0 m M, which was consistent with the previously reported millimolar Km of GLUT‐1 in erythrocyte model systems. Previously reported and reanalyzed quantification provided consistent kinetic parameters. We conclude that cerebral glucose transport is most consistently described when using reversible Michaelis‐Menten kinetics.