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.