Regional Blood—Brain Glucose Transfer in the Rat: A Novel Double-Membrane Kinetic Analysis

Abstract

Summary: Regional blood-brain glucose transfer was studied in pentobarbitone-anaesthetized rats using a pro grammed intravenous infusion technique that maintained steady levels of unlabeled (up to 55 mM) and tracer n-glucose in the circulating plasma. Regional cerebral blood flow, glucose phosphorylation rate, and tissue glu cose content were also measured under comparable con ditions. Data were analysed in terms of irreversible Mi chaelis -Menten kinetics assuming independent influx and efflux (Type I) and reversible Michaelis-Menten ki netics (Type II) across both the luminal and the abluminal membranes of the endothelial cell. The latter analysis corresponds to simple stereospecific membrane pores. The mathematical model allowed for changes in tissue glucose content and back-diffusion of tracer during the Glucose is transported across the blood-brain barrier principally by a process of facilitated diffu sion (Crone, 1965;Lund-Andersen, 1979).

Differentiation of Glucose Transport in Human Brain Gray and White Matter

“…3, the essential difference is that the individual fluxes J in and J out are reversible. It has been shown (Cunningham et al, 1986;Gruetter et al, 1998;Mahler and Cordes, 1971) that this change amounts to replacing the Michaelis-Menten constant K m with a product dependent term K m + [Glc]. This can be interpreted as a product-inhibited Michaelis-Menten model, in which, for instance, the forward reaction (uptake of glucose) is inhibited when brain glucose is present.…”

“…Recently, Gruetter et al (1998) proposed describing glucose transport kinetics across the human blood-brain barrier by a reversible Michaelis-Menten model (Cunningham et al, 1986;Mahler and Cordes, 1971). Although the model can also be visualized by Eq.…”

“…The exact gray and white matter composition of each voxel was established by quantitative T 1 relaxation imaging. The results were fitted with both the conventional Michaelis-Menten model (Lund-Andersen, 1979) and the reversible kinetic model of glucose transport (Cunningham et al, 1986;Mahler and Cordes, 1971) to obtain parameters for human cerebral gray and white matter. The reversible Michaelis-Menten transport model has recently been used to describe glucose transport across the human blood-brain barrier .…”

Localization of brain endothelial luminal and abluminal transporters with immunogold electron microscopy

“…It was generally accepted that blood-to-brain influx, and brain-toblood efflux of glucose were equal (or symmetrical). 49 -52 Cunningham et al 51 considered the possibility that BBB glucose transport could be kinetically analyzed in terms of translocation through a single membrane, or alternatively via individually (asymmetric) luminal and abluminal membranes. From these double-membrane mathematical analyses of brain glucose transport in modulated states (wherein anesthetized and conscious animals, or control and kainate-treated rats were compared) asymmetric distributions of capillary glucose transporter were predicted.…”

“…From these double-membrane mathematical analyses of brain glucose transport in modulated states (wherein anesthetized and conscious animals, or control and kainate-treated rats were compared) asymmetric distributions of capillary glucose transporter were predicted. 48,51,53 Immunogold electron microscopic studies, using antisera to the GLUT1 glucose transporter, were used to study the subcellular distribution of transporter protein in the BBB. 17,54 -56 In dog brain capillaries, Gerhart et al 54 observed a symmetrical distribution of GLUT1 epitopes between the luminal and abluminal membranes.…”