Effect of sorbinil and ascorbic acid on myo-inositol transport in cultured rat Schwann cells exposed to elevated extracellular glucose.

Abstract

The effect of long-term (2 weeks) exposure to 0-50 mM glucose and 0-1 mM sorbitol on myo-inositol metabolism was studied in cultured rat Schwann cells. Experiments were carried out to determine the effect of sorbinil and ascorbic acid on myo-inositol uptake in rat Schwann cells cultured in the presence of increased extracellular glucose or sorbitol. myo-Inositol uptake and its incorporation into phospholipids decreased significantly when cells were grown in > or = 30 mM glucose for a period of 2 weeks. This inhibitory effect was partly blocked by sorbinil, an aldose reductase inhibitor, in a dose-dependent fashion. Significant prevention was achieved with 0.5 and 1 mM sorbinil. Ascorbic acid also prevented the reduction in myo-inositol uptake due to excess extracellular glucose, at 3 and 30 microM concentrations, but not at 300 microM. Neither sorbinil nor ascorbic acid could prevent the alterations in myo-inositol transport in cells exposed to high sorbitol levels for the same period of time. These data suggest that glucose-induced alteration of myo-inositol transport in Schwann cells is mediated, at least in part, via sorbitol accumulation. This myo-inositol transport impairment is prevented by sorbinil and also by ascorbic acid. Ascorbic acid may hold a fresh promise for the treatment/prevention of diabetic neuropathy/complications, at least as an adjunct therapy along with known aldose reductase inhibitors.