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 transendoth elial transport of glucose is facilitated by a stereospecific, not ene rgy dependent carrier which can be saturated and shows transport compe tition among hexoses. Regulation of this transport capacity is an impo rtant adaptation mechanism for glucose supply to the brain, and most e xperimental data supports the notion that a decrease in blood glucose for several days induces an increase in BBB transport capacity, but hu man studies are few and contradictory Using the intravenous double-ind icator method, we studied BBB glucose transport following 3 days of st arvation in humans and found a significant 55% increase in the permeab ility-surface area product from blood to brain (PS1). This increase wa s expected due to the decrease in blood glucose level, but of a greate r magnitude than would be expected from known Michaelis-Menten paramet ers in humans. This finding indicates that following a few days of sta rvation in humans, BBB glucose transport may undergo adaptation. In an alogy with hypoglycemia, in healthy subjects rendered acutely hypergly cemic PS1 was reduced compared to a control group. However, this decre ase 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 wer e demonstrated in acute hyperglycemia, and this finding is in line wit h experimental data. At present, although human studies are few it see ms 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.