Neurobarrier coupling in the brain: adjusting glucose entry with demand.
Glucose transport over the blood-brain barrier (BBB) is a nonrate-limiting step and has therefore received little attention as a possible adjustment point within the transport reaction cascade from blood glucose to brain cell glycolysis. Considerations of the normal working point of facilitated BBB glucose shuttling via the GLUT-1 protein indicate that the transport is working at about one-third of T(max) under basal conditions. Substitution of T(max) estimates indicates that the transport is then just enough to keep up with glucose consumption, maintaining the steady state. After brain activation, glucose transport has to be stimulated, and this can be accomplished by increasing the driving force or changing the T(max) and/or K(t) parameters of BBB transport. The first possibility involves a decrease of brain interstitial glucose with subsequent flow stimulation according to the law of mass action (LMA), whereas the second possibility involves signaling from activated neurons to the BBB, a regulation loop that we propose to be called "neurobarrier coupling" (NBC). Theoretical analysis of the LMA effect and comparison with data on glucose dynamics during brain activation suggest that this factor alone only covers about half of the stimulation necessary to bring glucose delivery into line with the elevated glucose consumption during activation. Adjusting glucose entry with demand thus probably involves both LMA and NBC effects, depending on the degree of brain activation. Further work is needed to demonstrate NBC effects following physiological brain activation in vivo and to identify the signals that lead to NBC in in vitro experiments.
Leybaert
Luc
L
Department of Physiology and Pathophysiology, Faculty of Medicine and Health Sciences, Ghent University, Ghent, Belgium. luc.leybaert@ugent.be
De Bock
Marijke
M
Van Moorhem
Marijke
M
Decrock
Elke
E
De Vuyst
Elke
E
D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology; D001921:Brain / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006801:Humans
D005947:Glucose