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.