Blood-brain barrier transport of glucose: Adaptation to changes in blood glucose levels

Under normal physiological conditions, glucose is the major metabolic fuel in the brain, and the blood-brain barrier (BBB) is the major rate-limiting step for glucose entry into the human brain. The transendothelial transport of glucose is facilitated by a stereospecific, not energy dependent carrier which can be saturated and shows transport competition among hexoses. Regulation of this transport capacity is an important adaptation mechanism for glucose supply to the brain, and most experimental data supports the notion that a decrease in blood glucose for several days induces an increase in BBB transport capacity, but human studies are few and contradictory Using the intravenous double-indicator method, we studied BBB glucose transport following 3 days of starvation in humans and found a significant 55% increase in the permeability-surface area product from blood to brain (PS1). This increase was expected due to the decrease in blood glucose level, but of a greater magnitude than would be expected from known Michaelis-Menten parameters in humans. This finding indicates that following a few days of starvation in humans, BBB glucose transport may undergo adaptation. In analogy with hypoglycemia, in healthy subjects rendered acutely hyperglycemic PS1 was reduced compared to a control group. However, this decrease was not significant, and could be fully explained by the increase in blood glucose. We conclude that no changes in T-max, K-t or K-d were demonstrated in acute hyperglycemia, and this finding is in line with experimental data. At present, although human studies are few it seems that neither acute nor chronic hyperglycemia lend to adaptation in BBB glucose transport, whereas BBB transport seems upregulated after a few days of hypoglycemia. (C)1997, Medikal Press.