Uptake of glucose analogues into cultured cerebral microvessel endothelium.
Tritiated glucose analogues 3-O-methylglucose (3-OMG) and 2-deoxyglucose (2-DG) were used to study glucose uptake properties in established lines of cultured mouse cerebral microvessel endothelium. Uptake of both analogues was similar in terms of rate and absolute amount for the first two minutes. Thereafter, intracellular accumulation of 2-DG continued at a more rapid rate because of intracellular phosphorylation of this substrate. The uptake of 3-OMG uptake was temperature-dependent, independent of Na+, and not inhibited by ouabain or 2,4-dinitrophenol. Phloretin and cytochalasin B both significantly inhibited 3-OMG uptake. Other hexoses in high concentration acted as competitive inhibitors at the endothelial cell membrane. Pre-incubation of cells with 50 mM D-glucose resulted in higher levels of 3-OMG accumulation than in control cells (counter-transport phenomenon). In contrast to findings at the blood-brain barrier in vivo, insulin was found to stimulate 3-OMG uptake. Maximal stimulation of approximately 3-fold was found at ambient insulin concentrations of 1,000 ng/ml or higher. The findings provide support at the cellular level for some components of the model of carrier-mediated glucose transport across the blood-brain barrier which has been postulated to exist in vivo. The effect of insulin is discussed in the light of new data that show stimulation of glucose analogue transport into isolated cerebral capillaries.
D019325:3-O-Methylglucose; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology; D001692:Biological Transport / Q000187:drug effects; D001921:Brain / Q000098:blood supply*; D002460:Cell Line; D003837:Deoxy Sugars / Q000378:metabolism*; D003847:Deoxyglucose / Q000378:metabolism*; D004727:Endothelium / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D006601:Hexoses / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008757:Methylglucosides / Q000378:metabolism*; D008759:Methylglycosides / Q000378:metabolism*; D051379:Mice; D008833:Microcirculation / Q000378:metabolism; D010766:Phosphorylation
D000963:Antimetabolites; D003837:Deoxy Sugars; D006601:Hexoses; D007328:Insulin; D008757:Methylglucosides; D008759:Methylglycosides; D019325:3-O-Methylglucose; D003847:Deoxyglucose; D005947:Glucose