Inhibition by dexamethasone of the in vitro transport of 3-O-methylglucose into rat thymocytes.
Reduced glucose transport across the plasma membrane and reduced phosphorylation may both be responsible for the early inhibitory effect of physiological concentrations of glucocorticoids on glucose uptake by rat thymocytes. The early inhibitory effects of glucocorticoids (5 . 10(-7) M dexamethasone) on glucose consumption and 14CO2 formation from D-[U-14C]glucose were reproduced. The total uptake curve of 4.8 microM 3-O-[14C]methyl-D-glucose was biexponential with t 1/2 of 1.1 min and 36 min, respectively, the rapid part comprising about 50% of the equilibrated intracellular water space. The latency of the effect of 5 . 10(-7) M dexamethasone on 3-O-[14C]methyl-D-glucose uptake ranged from 15 to 100 min and the inhibition varied from 15 to 55% independently of the lag period. The effect of 3-O-methylglucose concentration on the initial uptake by steroid-responsive cell preparations was tested after 45 min of preincubation with or without 5 . 10(-7) M dexamethaone. In 12 experiments dexamethasone reduced V from 1.36 +/- 0.16 mmol . min-1 . l-1 cell water to 0.81 +/- 0.10 mmol . min-1 . l-1 cell water with insignificant change of Km (6.0 mM versus 5.9 mM). Dexamethasone had similar effect after 90 or 120 min. The variabilities of control cell transport capacity, the lag period and the magnitude of the dexamethasone effect could not be accounted for by changes in pH, effects of cell density, concentrations of albumin, ethanol, nucleosides, pyruvate or correlated to age and sex of the rats. In conclusion the inhibition of glucocorticoids on glucose consumption by thymocytes appears to be an inhibited plasma membrane transport capacity.
D000315:Adrenalectomy; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D005260:Female; D005947:Glucose / Q000378:metabolism; D007700:Kinetics; D008757:Methylglucosides / Q000378:metabolism*; D008759:Methylglycosides / Q000378:metabolism*; D051381:Rats; D013950:Thymus Gland / Q000187:drug effects / Q000378:metabolism*
D008757:Methylglucosides; D008759:Methylglycosides; D003907:Dexamethasone; D005947:Glucose