Steady-state cerebral glucose concentrations and transport in the human brain.
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 mM, the brain glucose level was a linear function of plasma glucose concentration. At plasma concentrations nearing 30 mM, the brain glucose level approached 9 mM, which was significantly higher than predicted from the previously reported Kt of approximately 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 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 mM, 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.
Gruetter
R
R
Department of Radiology, Center for MR Research and Clinical Research Center, University of Minnesota, Minneapolis 55455, USA.
Ugurbil
K
K
Seaquist
E R
ER
D000328:Adult; D001692:Biological Transport / Q000502:physiology; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D007700:Kinetics; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008875:Middle Aged; D008954:Models, Biological; D009994:Osmolar Concentration
D005947:Glucose