Blood-brain barrier permeability of glucose and ketone bodies during short-term starvation in humans. Hasselbalch, Steen G., Gitte M. Knudsen, Johannes Jakobsen, Lars Pinborg Hageman, Sren Holm, and Olaf B. Paulson. Department of Neurology, and Department of Nuclear Medicine, University Hospital, Rigshospitalet, Copenhagen, and Department of Neurology, Aarhus University Hospital, Aarhus, Denmark
APStracts 2:0048E, 1995.
The blood-brain barrier (BBB) permeability for glucose and [beta] -hydroxybutyrate ([beta]-OHB) was studied by the intravenous double -indicator method in 9 healthy subjects before and after 3.5 days of starvation. In fasting, mean arterial plasma glucose decreased from 5.41 +/-0.91 mM (mean +/- 1 SD) to 3.45 +/-0.33 mM (p<0.01), arterial concentration of [beta]-OHB increased from 0.23 +/-0.20 mM to 2.94 +/-0.84 mM (p<0.01), whereas cerebral blood flow remained unchanged. The permeability-surface area for BBB glucose transport from blood to brain, PS1, increased by 55 +/-31% from 0.076 +/-0.010 to 0.113 +/-0.019 (p<0.02), whereas no significant change in the permeability from brain back to blood, PS2, was found (0.121 +/-0.035 vs. 0.172 +/-0.109). PS1 for [beta]-OHB remained constant during starvation. The expected increase in PS1 due to the lower plasma glucose concentration was calculated to be 22% using previous estimates of Tmax and Kt for glucose transport. The determined increase was thus 33% higher than the expected increase and can only be partially explained by the decrease in plasma glucose. It is concluded that a modest upregulation of glucose transport across the BBB takes place following starvation. Brain transport of [beta]-OHB did not decrease as expected from the largely increased [beta]-OHB arterial level. This might be interpreted as an increase in brain transport of [beta]-OHB which could be caused by induction mechanisms but the large non-saturable component of [beta]-OHB transport makes such a conclusion difficult. However, both [beta]-OHB blood concentration and [beta]-OHB influx into the brain increased by more than 10 times. This implies that the influx of ketone bodies into the brain is largely determined by the amount of ketones present in the blood and any condition in which ketonemia occurs will lead to an increased ketone influx. 

Received 19 July 1994; accepted in final form 30 January 1995.
APS Manuscript Number E271-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 21 March 1995.