Expression and characterization of the sugar transporter, Glut 5 in microglial cells of the human and rat brain

Abstract

All mammalian cells utilize and metabolize glucose for energy production. Glucose is transported into the cell by members of the family of facilitative glucose transporters, Glut 1-6. Each glucose transporter is cell and tissue specific, and is regulated by either glucose or hormonal stimuli such as insulin. The brain expresses Glut 1-6. Glut 1 is expressed in endothelial cells of the blood brain barrier, Glut 2 is expressed in astrocytes. Glut 3 is expressed in neuronal cells and Glut 4 is expressed in the granule cells of the cerebellum. We have reported that Glut 5 is exclusively expressed in microglial cells in the brain. We were the first to demonstrate the cellular specificity of Glut 5 in the brain. The expression of this transporter in the brain is intriguing. Glut 5 has a very low affinity for glucose, and studies in Xenopus oocytes have shown that Glut 5 functions as a fructose transporter. However, the brain has insignificant concentrations of fructose for transport by Glut 5, and therefore it is unlikely that Glut 5 functions as a fructose transporter in brain. In order to further characterize Glut 5 expression in microglia, the expression pattern, regulation and subcellular localization of Glut 5 were studied in human and rat brain tissue and in cultured cells. These studies demonstrate: that Glut 5 is exclusively expressed in microglia in both human and rat brain. However, Glut 5 is not expressed in all microglial cells; an undefined subset of microglia express Glut 5 in both tissue and in culture. We have also shown that Glut 5 is not a plasma membrane protein but rather is in vesicle-like structures within the cell. In addition we have demonstrated that Glut 5, like other facilitative glucose transporters, can be regulated by glucose concentrations. Finally, levels of Glut 5 appear to be altered in Alzheimer's disease, a condition in which glucose transport and metabolism are affected. In conclusion, the expression of Glut 5 in the brain, an organ with insignificant concentrations of fructose, implies that Glut 5 has an alternate function in the CNS. Our goal was to characterize the cellular expression of Glut 5 in the brain and to determine the factors which regulate Glut 5 expression in these unidentified cells.