Effect of glucose and an aldose reductase inhibitor on myo-inositol uptake by cultured human endothelial cells.
The effects of an aldose reductase (AR) inhibitor, elevated glucose and other compounds were evaluated on in vitro 2-[3H] myo-inositol (MI) uptake in cultured human endothelial cells (ECs). Significant AR activity was present in ECs (1,373 +/- 170 mumol/mg.min: incubated with 28 mM glucose for 48 hr). Since Na(+)-deprivation and the addition of Ouabain (5 mM) significantly reduced MI uptake, MI incorporation into ECs might be dependent on an active transport system via Na(+)-K+ ATPase activity. MI uptake was reduced significantly (21 +/- 6, 39 +/- 7% reduction) in the presence of excess glucose (27.5, 55 mM). However, addition of the AR inhibitor (ONO-2235 100 microM) prevented the glucose mediated inhibition of MI uptake (15 +/- 5, 21 +/- 6% reduction). These results suggest that inhibition of AR might prevent glucose-mediated toxicity via an increment of MI uptake.
Okuda
Y
Y
Department of Internal Medicine, University of Tsukuba, Ibaraki, Japan.
Bannai
C
C
Nagahama
M
M
Mizutani
M
M
Mitsui
Y
Y
Yamashita
K
K
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007294:Inositol / Q000378:metabolism*; D007700:Kinetics; D008353:Mannitol / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D053778:Thiazolidines; D014471:Umbilical Veins
D053778:Thiazolidines; D008353:Mannitol; C038131:epalrestat; D007294:Inositol; D010042:Ouabain; D012236:Rhodanine; D000449:Aldehyde Reductase; D005947:Glucose