Trans-hydroxyl group configuration on carbons 2 and 3 of glucose. Responsible for acute inhibition of myo-inositol transport?
Cultured neuroblastoma, cerebral microvessel endothelial, and retinoblastoma cells were used to examine the mechanism of acute inhibition by D-glucose of myo-inositol uptake. Acute exposure of the cells to 30 mM D-glucose caused a significant decrease in Na(+)-dependent myo-inositol uptake in all three cell types. The effect of D-glucose to acutely inhibit myo-inositol uptake was dependent on the extracellular glucose concentration and was not reversed by sorbinil. 2-Deoxy-D-glucose (30 mM), 3-O-methyl-D-glucose (30 mM), and cytochalasin B (100 microM) did not acutely inhibit myo-inositol uptake. These data suggest that the hydroxyl groups on carbons 2 and 3 of D-glucose, which in a Haworth projection appear trans to each other, are important for inhibitory activity. Other monosaccharides (30 mM) having a similar 2,3-trans-diol configuration, L-glucose, D- and L-fucose, D- and L-galactose, D- and L-xylose, and D-arabinose, all to varying degrees significantly inhibited myo-inositol uptake. In all cases, the L-isomers were more potent inhibitors of myo-inositol uptake than the corresponding D-isomers. Monosaccharides (30 mM) having hydroxyl groups on carbons 2 and 3 in a cis configuration, D-mannose, L-rhamnose, D-allose, and D-ribose, did not acutely inhibit myo-inositol uptake. Replacing the hydroxyl group with a fluorine on carbons 2 or 3 of D-glucose negated its inhibitory activity of myo-inositol uptake. In contrast, replacing the hydroxyl group with a fluorine on carbon 6 of D-glucose did not block its inhibition of myo-inositol uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
Yorek
M A
MA
Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, IA 52246.
Stefani
M R
MR
Dunlap
J A
JA
Ro
K S
KS
Davidson
E P
EP
D019325:3-O-Methylglucose; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002236:Carbohydrate Conformation; D002460:Cell Line; D003571:Cytochalasin B / Q000494:pharmacology; D003847:Deoxyglucose / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D005947:Glucose / Q000737:chemistry / Q000494:pharmacology*; D007294:Inositol / Q000737:chemistry / Q000378:metabolism*; D007700:Kinetics; D008757:Methylglucosides / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D009447:Neuroblastoma; D010695:Phlorhizin / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology
D008757:Methylglucosides; D019325:3-O-Methylglucose; D003571:Cytochalasin B; D007294:Inositol; D003847:Deoxyglucose; D012964:Sodium; D010695:Phlorhizin; D005947:Glucose