title: Differentiation of glucose transport in human brain gray and white matter.
abstract: Localized 1H nuclear magnetic resonance spectroscopy has been applied to determine human brain gray matter and white matter glucose transport kinetics by measuring the steady-state glucose concentration under normoglycemia and two levels of hyperglycemia. Nuclear magnetic resonance spectroscopic measurements were simultaneously performed on three 12-mL volumes, containing predominantly gray or white matter. The exact volume compositions were determined from quantitative T1 relaxation magnetic resonance images. The absolute brain glucose concentration as a function of the plasma glucose level was fitted with two kinetic transport models, based on standard (irreversible) or reversible Michaelis-Menten kinetics. The steady-state brain glucose levels were similar for cerebral gray and white matter, although the white matter levels were consistently 15% to 20% higher. The ratio of the maximum glucose transport rate, V(max), to the cerebral metabolic utilization rate of glucose, CMR(Glc), was 3.2 +/- 0.10 and 3.9 +/- 0.15 for gray matter and white matter using the standard transport model and 1.8 +/- 0.10 and 2.2 +/- 0.12 for gray matter and white matter using the reversible transport model. The Michaelis-Menten constant K(m) was 6.2 +/- 0.85 and 7.3 +/- 1.1 mmol/L for gray matter and white matter in the standard model and 1.1 +/- 0.66 and 1.7 +/- 0.88 mmol/L in the reversible model. Taking into account the threefold lower rate of CMR(Glc) in white matter, this finding suggests that blood--brain barrier glucose transport activity is lower by a similar amount in white matter. The regulation of glucose transport activity at the blood--brain barrier may be an important mechanism for maintaining glucose homeostasis throughout the cerebral cortex.
authors.affiliation: Department of Radiology, Yale University, School of Medicine, New Haven, Connecticut 06520-8043, USA.
authors.forename: R A
authors.initials: RA
authors.lastname: de Graaf
authors.forename: J W
authors.initials: JW
authors.lastname: Pan
authors.forename: F
authors.initials: F
authors.lastname: Telang
authors.forename: J H
authors.initials: JH
authors.lastname: Lee
authors.forename: P
authors.initials: P
authors.lastname: Brown
authors.forename: E J
authors.initials: EJ
authors.lastname: Novotny
authors.forename: H P
authors.initials: HP
authors.lastname: Hetherington
authors.forename: D L
authors.initials: DL
authors.lastname: Rothman
mesh_terms: D000328:Adult; D001692:Biological Transport; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D006943:Hyperglycemia / Q000378:metabolism; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D008297:Male
chemical_list: D001786:Blood Glucose; D005947:Glucose