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Translocable Glucose Transporters in the Brain

The discovery of the brain expression of the translocable glucose transporters, GLUT4 then GLUT8, led to the question of their putative role in the central nervous system, particularly in relation to insulin effect. The anatomical, cellular, and subcellular localization of these transporters has been described in detail. It has been shown that, as in peripheral tissues, these transporters are localized both in an intracellular pool and at the plasma membrane. This is coherent with a translocation phenomenon, but the data reporting the effect of insulin on that property of GLUT4 and GLUT8 remains very controversial. Glucose and insulin have been shown to modulate GLUT4 expression. Based on their anatomical features, different hypotheses have been proposed. Because of the colocalization with the insulin receptors, insulin might regulate glucose uptake in specific brain areas. A role in nutrient sensing has also been proposed, since both insulin and GLUT4 are expressed in gluco-excited neurons of the hypothalamus. Some studies suggest a role for GLUT8 in the endoplasmic reticulum stress. Whereas much has been learned about their cellular features in the central nervous system, many questions remain unanswered concerning their physiological functions. Gene knockout strategy specifically in the brain and even more in specific nuclei or type of cells should provide new clues to the physiological role of both transporters in the central nervous system.