1H NMR studies of glucose transport in the human brain.
The difference between 1H nuclear magnetic resonance (NMR) spectra obtained from the human brain during euglycemia and during hyperglycemia is depicted as well-resolved glucose peaks. The time course of these brain glucose changes during a rapid increase in plasma glucose was measured in four healthy subjects, aged 18-22 years, in five studies. Results demonstrated a significant lag in the rise of glucose with respect to plasma glucose. The fit of the integrated symmetric Michaelis-Menten model to the time course of relative glucose signals yielded an estimated plasma glucose concentration for half maximal transport, Kt, of 4.8 +/- 2.4 mM (mean +/- SD), a maximal transport rate, Tmax, of 0.80 +/- 0.45 micromol g-1 min-1, and a cerebral metabolic glucose consumption rate (CMR)glc of 0.32 +/- 0.16 micromol g-1 min-1. Assuming cerebral glucose concentration to be 1.0 micromol/g at euglycemia as measured by 13CMR, the fit of the same model to the time course of brain glucose concentrations resulted in Kt = 3.9 +/- 0.82 mM, Tmax = 1.16 +/- 0.29 micromol g-1 min-1, and CMRglc = 0.35 +/- 0.10 micromol g-1 min-1. In both cases, the resulting time course equaled that predicted from the determination of the steady-state glucose concentration by 13C NMR spectroscopy within the experimental scatter. The agreement between the two methods of determining transport kinetics suggests that glucose is distributed throughout the entire aqueous phase of the human brain, implying substantial intracellular concentration.
Gruetter
R
R
Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, Connecticut, USA.
Novotny
E J
EJ
Boulware
S D
SD
Rothman
D L
DL
Shulman
R G
RG
D000293:Adolescent; D000328:Adult; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D001812:Blood-Brain Barrier; D001921:Brain / Q000378:metabolism*; D005110:Extracellular Space / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008954:Models, Biological; D009994:Osmolar Concentration; D011522:Protons; D013997:Time Factors; D014018:Tissue Distribution
D001786:Blood Glucose; D011522:Protons; D005947:Glucose