Effects of dexamethasone in vivo and in vitro on hexose transport in brain microvasculature.
Glucocorticoids induce hyperinsulinemia, hyperglycemia, and depress glucose transport by aortic endothelium. High glucocorticoid doses are used for many diseases, but with unknown effects on brain glucose transport or metabolism. This study tested the hypothesis that glucocorticoids affect glucose transport or metabolism by brain microvascular endothelium. Male rats received dexamethasone (DEX) s.c. with sucrose feeding for up to seven days. Cerebral microvessels from rats treated with DEX/sucrose demonstrated increased GLUT1 and brain glucose extraction compared to controls. Glucose transport in vivo correlated with hyperinsulinemia. Pre-treatment with low doses of streptozotocin blunted hyperinsulinemia and prevented increased glucose extraction induced by DEX. In contrast, isolated brain microvessels exposed to DEX in vitro demonstrated suppression of 2-deoxyglucose uptake and glucose oxidation. We conclude that DEX/sucrose treatment in vivo increases blood-brain glucose transport in a manner that requires the effects of chronic hyperinsulinemia. These effects override any direct inhibitory effects of either hyperglycemia or DEX.
Chipkin
S R
SR
Department of Medicine, Boston University School of Medicine, MA 02118, USA.
van Bueren
A
A
Bercel
E
E
Garrison
C R
CR
McCall
A L
AL
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002560:Cerebrovascular Circulation / Q000187:drug effects / Q000502:physiology*; D003907:Dexamethasone / Q000494:pharmacology*; D019422:Dietary Sucrose; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D006601:Hexoses / Q000378:metabolism*; D006946:Hyperinsulinism / Q000378:metabolism / Q000503:physiopathology; D007328:Insulin / Q000097:blood; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology*; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013311:Streptozocin / Q000494:pharmacology
D001786:Blood Glucose; D019422:Dietary Sucrose; D051272:Glucose Transporter Type 1; D006601:Hexoses; D007328:Insulin; D009004:Monosaccharide Transport Proteins; C495679:Slc2a1 protein, rat; D013311:Streptozocin; D003907:Dexamethasone; D005947:Glucose