EFFECT OF SORBINIL AND ASCORBIC-ACID ON MYOINOSITOL TRANSPORT IN CULTURED RAT SCHWANN-CELLS EXPOSED TO ELEVATED EXTRACELLULAR GLUCOSE

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 Sch wann cells. Experiments were carried out to determine the effect of so rbinil and ascorbic acid on myo-inositol uptake in rat Schwann cells c ultured in the presence of increased extracellular glucose or sorbitol . myo-Inositol uptake and its incorporation into phospholipids decreas ed significantly when cells were grown in greater than or equal to 30 mM glucose for a period of 2 weeks. This inhibitory effect was partly blocked by sorbinil, an aldose reductase inhibitor, in a dose-dependen t fashion. Significant prevention was achieved with 0.5 and 1 mM sorbi nil. Ascorbic acid also prevented the reduction in myo-inositol uptake due to excess extracellular glucose, at 3 and 30 mu M concentrations, but not at 300 mu M. Neither sorbinil nor ascorbic acid could prevent the alterations in myo-inositol transport in cells exposed to high so rbitol levels for the same period of time. These data suggest that glu cose-induced alteration of myo-inositol transport in Schwann cells is mediated, at least in part, via sorbitol accumulation. This myo-inosit ol transport impairment is prevented by sorbinil and also by ascorbic acid. Ascorbic acid may hold a fresh promise for the treatment/prevent ion of diabetic neuropathy/complications, at least as an adjunct thera py along with known aldose reductase inhibitors.