The glucose transporter of the human brain and blood‐brain barrier

Abstract

We identified and characterized the glucose transporter in the human cerebral cortex, cerebral microvessels, and choroid plexus by specific D-glucose-displaceable [3H]cytochalasin B binding. The binding was saturable, with a dissociation constant less than 1 microM. Maximal binding capacity was approximately 7 pmol/mg protein in the cerebral cortex, approximately 42 pmol/mg protein in brain microvessels, and approximately 27 pmol/mg protein in the choroid plexus. Several hexoses displaced specific [3H]cytochalasin B binding to microvessels in a rank-order that correlated well with their known ability to cross the blood-brain barrier; the only exception was 2-deoxy-D-glucose, which had much higher affinity for the glucose transporter than the natural substrate, D-glucose. Irreversible photoaffinity labeling of the glucose transporter of microvessels with [3H]cytochalasin B, followed by solubilization and polyacrylamide gel electrophoresis, labeled a protein band with an average molecular weight of approximately 55,000. Monoclonal and polyclonal antibodies specific to the human erythrocyte glucose transporter immunocytochemically stained brain blood vessels and the few trapped erythrocytes in situ, with minimal staining of the neuropil. In the choroid plexus, blood vessels did not stain, but the epithelium reacted positively. We conclude that human brain microvessels are richly endowed with a glucose transport moiety similar in molecular weight and antigenic characteristics to that of human erythrocytes and brain microvessels of other mammalian species.

Quantitative Immunocytochemical Study of Blood-Brain Barrier Glucose Transporter (GLUT-1) in Four Regions of Mouse Brain

“…More complex, however, is the problem of the localization of GLUT-1 in the choroid plexus. Our observations indicating negligible immunoreactivity of the vascular fenestrated endothelium and distinct labeling of the undulated basolateral membrane of the epithelial cells, with absence of immunolabeling of apical plasmalemma and intercellular junctions, are compatible with those obtained in mice, rats, and rabbits by other authors (Kalaria et al 1988;Harik et al 1990;Farrell et al 1992;Cornford et al 1995;Bolz et al 1996). Nevertheless, they differ from recent observations of Cornford et al (1998) indicating an abundance of GLUT-1 immunoreactivity in the vascular fenestrated endothelium and in the basolateral membranes of the epithelial cells of human (biopsy specimens) and nonhuman primate choroid plexi.…”

B-vitamin deficiency causes hyperhomocysteinemia and vascular cognitive impairment in mice

“…RDI-GLUT1, Research Diagnostics), which specifically labels capillaries and not larger vessels (55,56). Microglia were labeled with a monoclonal rat antibody against cell surface protein CD11b/Mac-1, which is expressed by all brain microglia (catalog no.…”

GLUT1 deficiency and other glucose transporter diseases

“…The GLUT1 protein in the erythrocyte membrane is immunologically and chemically identical to the GLUT1 isoform in cerebral microvessels (26). The rate of 3-O-methyl-D-glucose uptake by freshly isolated, washed erythrocytes in vitro is decreased in patients compared with controls.…”