Glucose transport into brain: Effects of hypoglycemia

In summary, substantial experimental evidence now clearly supports an increase in brain glucose uptake as a primary compensation to prevent the deleterious effects of ongoing hypoglycemia. The results of several studies, including the ones reported here, suggest that the primary adaptation occurs at the level of the regulation of glucose transport through the increased expression of GLUT1 mRNA and protein in the microvascular endothelial cells that comprise the BBB. The extent to which this involves direct transcriptional activation, or perhaps an increased mRNA stability remains to be determined. In addition to increased GLUT1 synthesis, a post-translational mechanism to augment glucose uptake involves the redistribution of transporters across the endothelial cell with an increased transport capacity at the luminal surface of the BBB. At the same time, the lack of a demonstrable effect on either the glial 45 kDa GLUT1, or the neuronal GLUT3, further suggests that the BBB is indeed the "gatekeeper" to glucose delivery to the brain, sensitive enough to respond to even moderate levels of hypoglycemia. The potential downside of this adaptation is that the increased ability to transport glucose lowers the threshold for sensing hypoglycemia, ie hypoglycemia-unawareness, and delays the onset of the counterregulatory response which now constitutes the major complication of tight control in diabetes.