Glucose metabolism is depressed in the temporal and parietal regions of the cortex in patients with Alzheimer's disease. We measured the concentrations of two glucose transporters, GLUT1 and GLUT3, in six regions of brains from both control subjects and patients with Alzheimer's disease. The concentrations of both transporters were reduced in the cerebral cortex, with larger and highly significant reductions observed for GLUT3, the putative neuronal glucose transporter. The reductions in GLUT3 were greater than the loss of synapses, and should be considered as a potential cause of the deficits in glucose metabolism.

We examined the immunohistochemical localization of Glut 1 in sections of developing rat brain [gestational (G) days 18 and 20, postnatal (P) days 1, 10, 21, and greater than 40; term = approximately G21] and characterized the abundance of Glut 1 in isolated brain microvessels by Western blot analysis. Further quantitation of total glucose transporters by [125I]3-iodo-4-azido-phenethyl-amido-7-O-succinyldeacetyl-forskoli n photoaffinity labeling was performed. Glut 1 was prominently distributed in G18 and P1 brain vascular endothelial cells, with comparatively little immunoreactivity observed in brain parenchyma. Conversely, at P10, Glut 1 was prominent in brain parenchyma (undifferentiated cells) and less evident in the vascular endothelium. However, at P21, a resurgence of Glut 1 in vascular endothelial cells was observed, as was a sustained presence in parenchymal cells. On P greater than 40, a distribution in vascular endothelial cells and, to a minor extent, in parenchymal perivascular stellate cells was noted. Microvessel preparation Glut 1 (approximately 55-60 kDa) and [125I] 3-iodo-4-azido-phenethyl-amido-7-O-succinyldeacetyl-forskolin photoaffinity-labeled glucose transporters gradually increased from G18 through P10 to P greater than 40. This developmental increase in Glut 1 was also seen in whole homogenates (approximately 45-47 kDa), but not in crude brain membranes. Thus, isolated microvascular preparations indicated that Glut 1 levels constantly increased with maturation, but direct visualization of brain sections revealed that the localization in different cellular compartments changed with development. These alterations in cellular localization of glucose transporters, appear to occur in concert with the changing glucose metabolic needs of the brain, which, during the various stages of development, exhibits constantly changing phases of cellular growth and proliferation.

We investigated the presence of three specific types of glucose transporters (GT) within the rabbit central nervous system during various developmental stages. Employing the Hep G2/brain-type insulin-insensitive and the insulin-responsive (IRGT; adipocyte/skeletal muscle type) GT antibody and cDNA, we studied protein and mRNA within the whole brain (25-, 27-, and 30-day-old fetus; 1-, 5-, 10-day-old neonate; and adult), using cultured neuronal and glial cells, by Western and Northern blot analysis. Similarly, using the insulin-insensitive human fetal skeletal muscle-type (GLUT-3) GT cDNA, we characterized this mRNA by Northern blot analysis. Additional confirmation of cell specificity was sought by performing immunohistochemical staining on the neuronal and glial cells to detect the specific type of GT protein. We observed a developmental regulation of brain-type GT within the whole brain, the peak abundance of protein and mRNA occurring in the adult, followed next by the fetus. No IRGT was detected within the whole brain at any stage of development. Contrary to the brain-type GT mRNA, GLUT-3 mRNA was found to be most abundant in the 10-day-old neonate and adult, followed next by the early neonate, with little in the fetus. Within isolated brain cell cultures, the mRNAs for the brain- and GLUT-3-types of GTs were abundantly present within glial cells, with considerably lesser amounts noted within the neurons. IRGT, on the other hand, revealed rather weak mRNA bands in both glial and neuronal cells. Western blotting revealed a brain type of GT protein within the glial cells alone; the neuronal cells for the most part were devoid of both the brain-type and the IRGT proteins. Further immunohistochemical staining confirmed the definite presence of the brain-type GT within the glial cells, with slight immunoreactivity observed within the neurons. Additionally, no significant IRGT immunoreactivity was observed within either cell type. We did not study the GLUT-3 type of immunoreactivity within neurons and glia. We conclude that both the Hep G2/brain and the GLUT-3 types, and not the IRGT, are developmentally regulated within the whole brain. Further, the Hep G2/brain and the GLUT-3 types of GTs are distinctly present within glial cells, with none to minute amounts present within the neurons. No IRGT protein is observed within the whole brain and the two cell types. These results suggest a differential expression of specific GT types within the neuronal and glial components of the brain.

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