Translocable Glucose Transporters in the Brain

Abstract

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. Diabetes 55 (Suppl. 2): S131-S138, 2006

Epigenetics and energetics in ventral hippocampus mediate rapid antidepressant action: Implications for treatment resistance

“…Here, the dysregulation in central insulin levels in FSL does not seem to involve the canonical mechanism of insulin resistance linked to Glut-4, which, instead, is up-regulated in the vDG of FSL, thereby suggesting that there may be an upstream mechanism in the insulin resistance associated with the depressive-like phenotype of FSL that could involve other glucose transporters, such as Glut-12. A similar link between insulin resistance and increased Glut-4 (27) was shown previously in hyperinsulemic-hyperglycemic rats, which show increased Glut-4 levels in the cerebellum (28). Future work should study whether Glut-4 changes may reflect a compensatory response to deficits in central glucose levels and to the hyperactivation of the glutamate and leptin systems.…”

Chronic Estradiol Treatment Improves Brain Homeostasis during Aging in Female Rats

“…51). Depending on the glycemia achieved during the hyperinsulinemic clamp, glucose uptake could be either increased or decreased in different brain areas (51). This could reasonably explain the different results observed for the Glut-4 levels in the cortex and the diencephalon of the various experimental groups in the current study (Fig.…”

“…Conversely, because Glut-4 immunoreactivity has been observed in an intracellular localization, this glucose transporter could be translocated to the plasma membrane; this translocation phenomenon could be controlled by metabolic and/or hormonal parameters (for a review, see Ref. 51). Depending on the glycemia achieved during the hyperinsulinemic clamp, glucose uptake could be either increased or decreased in different brain areas (51).…”

cAMP-dependent insulin modulation of synaptic inhibition in neurons of the dorsal motor nucleus of the vagus is altered in diabetic mice

“…Therefore, in hyperglycemic animals, there is likely an altered component of the insulin receptor cascade that interacts with the cAMP pathway. Neuronal GLUT4 is altered in diabetes, depending on brain region and diabetes model (2,3,16,19,33,34,54). Thus, one potential site of the dysfunction in diabetic mice is GLUT4 expression and/or translocation to the membrane.…”