In the present study we examined the expression and localization of Glut 3 in human brain using peptide-specific antisera. Glut 3 was expressed at 2-3 times higher levels in cerebral cortex from adult (n = 6) compared to that from neonatal infants (n = 4; P less than 0.05). However, similar levels of immunoreactive Glut 3 were present in cerebellum from adults (n = 6) and newborns (n = 4). Cellular localization of Glut 3 in adult (n = 5) and neonatal (n = 5) infant brains was undertaken by immunohistochemical analysis. Glut 3 was visible in the adult neuropil of the cerebral cortex; in certain cellular processes within the deeper cortical layers; in intravascular white cells, including monocytes, lymphocytes and granulocytes; and in microvascular endothelial cells. Neither the premature nor the mature newborn cerebral cortex exhibited Glut 3 labeling in the neuropil or microvasculature. In the cerebellum, given the stratified nature of the cellular arrangement, Glut 3 was more clearly and definitively noted in the cellular processes at all stages of development. Double labeling studies using neuronal (neurofilament) and astrocytic (glial fibrillary acidic protein) markers indicated that Glut 3 was primarily expressed in neurons. We conclude that Glut 3 is localized in many cellular components, including white blood cells in human brain. The prominent localization of Glut 3 to mature neuronal processes suggests an essential role for this transporter in regulating fuel requirements for dendritic and axonal traffic, thereby mediating neurotransmission. Further study is required to address the possibility that another as yet undefined glucose transporter isoform is expressed in other cell-specific regions of the brain.

The recently cloned Glut-5, glucose transporter isoform, is expressed in human jejunum and kidney. Employing previously characterized polyclonal antibodies directed towards the C-terminus region of the derived human Glut-5 peptide and Western blot analysis, a 50-55 kilodalton Glut-5 protein was detected in adult human brain homogenates. The amount of Glut-5 protein in brain was 4-fold lower when compared to the levels in adult kidney. Immunohistochemical analysis using cerebral and cerebellar sections demonstrated Glut-5 immunoreactivity in only some of the Glut-1 and factor VIII-positive brain microvascular endothelial cells, the intravascular red and white blood cells being negative. This selective localization pattern was confirmed by the 5-fold enrichment of Glut-5 vs. a 20-fold enrichment of Glut-1 in an isolated human cerebral cortical microvascular preparation, when compared to whole cerebral homogenates. We conclude that Glut-5 is localized in the endothelial cells of human brain microvasculature. Unlike other fructose using tissues, where Glut-5 may subserve the role of a fructose carrier, in brain where fructose is not used as a substrate, Glut-5 may transport glucose alone. This role of Glut-5 in conjunction with the previously characterized brain endothelial Glut-1 and Glut-3 needs further elucidation.

The expression of glucose transporter isoforms (Glut 1, Glut 3, Glut 4, and Glut 5) in the human eye was investigated at various ages ranging between 8 weeks gestation (first trimester) and adult using Western blot and immunohistochemical analyses. Glut 1 and Glut 3 expression and cellular localization patterns were similar to those of human brain. Glut 1 (50-kilodalton protein) was expressed by epithelial cells (retinal pigmented epithelium, choroidal, iridial, and pars planus), which form the blood-eye barrier, retinal Mueller cells, the lens fiber cells, iridial microvascular endothelial cells, and to a lesser extent by the outer segments of the photoreceptor cells in the adult eye. This pattern was conserved throughout development and was evident as early as 8 weeks gestation. In addition, the endothelial cells of vitreous hyaloid vessels expressed Glut 1 at 8 weeks gestation. Glut 3 (50 to 55-kilodalton protein) immunoreactivity was observed only in the adult inner synaptic layer of the retina. Neither Glut 4 nor Glut 5 was expressed in any occular tissue at any age examined. These results suggest that Glut 1 is the main glucose transporter of the human eye and that it is ontogenically conserved. In contrast, Glut 3 is associated with selective neuronal processes, and its expression is developmentally altered.

Two premature newborn infants developed extreme magnesium toxicity while receiving total parenteral nutrition (TPN) infusion. Both patients exhibited acute hypotonia, apnea, hypotension, and refractory bradycardia mimicking septic shock syndrome. The complete blood count was normal, and blood cultures were negative. Serum magnesium concentration in 1 patient was 43.1 mEq/L and in the other patient was 45 mEq/L (normal values for serum magnesium being 1.6-2.1 mEq/L). Hypermagnesemia resulted from malfunction of an automated TPN mixing device. Unexplained sudden onset of apnea, refractory bradycardia, and hypotension should raise suspicions of hypermagnesemia, a reversible condition if identified and treated early.

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