Glucose transporters in mammalian brain.

(;lucose is the primary energy source for mammalian brain and a continuous supply is vital for normal cerebral function. At rest, the brain is responsible for metabolizing up to 60% of the available circulating glucose, and the efficient transport of glucose across the blood-brain barrier (BRH) and into the various cells that make up the brain is essential. Of the six facilitative glucose transporter proteins that have been cloned [ 11, at least four have been detected in brain: GLUTS 1, 3, 5 and 7. The objective of this report is to describe the location of the various transporters and to provide a quantitative assessment of their relative concentrations. GLLJTl was the first transporter to be detected in brain when antibodies against the human erythrocyte glucose transporter were found to cross-react with the endothelial cells comprising the I jBH [Z]. A broad band of 55 k D a is detected by Western blot analysis of purified cerebral microvessels (Figure 1) [3] . GLUT1 protein is extremely concentrated in these cells and can be readily detected by immunohistochemical techniques [ 4-61, In combination with electron microscopy, such techniques have revealed an asymmetric protein distribution, with more transporters being detected in the abluminal membrane (brain side) than in the luminal membrane (blood side), and the presence of an intracellular pool of transporters (see a review by Partridge and Hoado [7]). A second isoform of GLUT1 with an apparent molecular mass of 45 kDa, can also be detected in whole brain by Western blotting (Figure 1). In terms of relative concentrations, this form appears to be 2-5-fold more concentrated than the 55 k I h form per unit mass brain membrane protein, depending on the region. However, with the exception of the choroid plexus and the occasional astrocyte [8,9], in our hands this form is extremely difficult to detect immunohistochemically. GLUT1 mRNA was detected only in microvessels in the earlier in situ hybridization studies [ 41. I Iowever, more recent studies by Hondy and colleagues [ 10,l I ] while confirming the intense labelling of the microvessels and choroid plexus have also shown a more general