Mechanisms of glucose transport at the blood-brain barrier: an in vitro study.
How the brain meets its continuous high metabolic demand in light of varying plasma glucose levels and a functional blood-brain barrier (BBB) is poorly understood. GLUT-1, found in high density at the BBB appears to maintain the continuous shuttling of glucose across the blood-brain barrier irrespective of the plasma concentration. We examined the process of glucose transport across a quasi-physiological in vitro blood-brain barrier model. Radiolabeled tracer permeability studies revealed a concentration ratio of abluminal to luminal glucose in this blood-brain barrier model of approximately 0.85. Under conditions where [glucose](lumen) was higher than [glucose](ablumen), influx of radiolabeled 2-deoxyglucose from lumen to the abluminal compartment was approximately 35% higher than efflux from the abluminal side to the lumen. However, when compartmental [glucose] were maintained equal, a reversal of this trend was seen (approximately 19% higher efflux towards the lumen), favoring establishment of a luminal to abluminal concentration gradient. Immunocytochemical experiments revealed that in addition to segregation of GLUT-1 (luminal>abluminal), the intracellular enzyme hexokinase was also asymmetrically distributed (abluminal>luminal). We conclude that glucose transport at the CNS/blood interface appears to be dependent on and regulated by a serial chain of membrane-bound and intracellular transporters and enzymes.
McAllister
M S
MS
Department of Neurological Surgery, Cerebrovascular Research Center, Cleveland Clinic Foundation/NB20, 9500 Euclid Avenue, Cleveland, OH 44195, USA.
Krizanac-Bengez
L
L
Macchia
F
F
Naftalin
R J
RJ
Pedley
K C
KC
Mayberg
M R
MR
Marroni
M
M
Leaman
S
S
Stanness
K A
KA
Janigro
D
D
D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000378:metabolism; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000502:physiology*; D002250:Carbon Radioisotopes / Q000493:pharmacokinetics; D002417:Cattle; D002451:Cell Compartmentation / Q000187:drug effects / Q000502:physiology; D002454:Cell Differentiation / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002463:Cell Membrane Permeability / Q000502:physiology; D002478:Cells, Cultured; D018920:Coculture Techniques; D003847:Deoxyglucose / Q000493:pharmacokinetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D005333:Fetus; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D006593:Hexokinase / Q000378:metabolism; D007150:Immunohistochemistry; D008567:Membranes, Artificial; D009004:Monosaccharide Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D010641:Phenotype; D051381:Rats
D002250:Carbon Radioisotopes; D051272:Glucose Transporter Type 1; D008567:Membranes, Artificial; D009004:Monosaccharide Transport Proteins; C495679:Slc2a1 protein, rat; D003847:Deoxyglucose; D006593:Hexokinase; D005947:Glucose