Effect of sorbinil and ascorbic acid on myo-inositol 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 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.
Karihaloo
A K
AK
Department of Neurology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Joshi
K
K
Chopra
J S
JS
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D000831:Animals, Newborn; D001205:Ascorbic Acid / Q000494:pharmacology*; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D007093:Imidazoles / Q000494:pharmacology*; D048289:Imidazolidines; D007294:Inositol / Q000378:metabolism*; D007700:Kinetics; D010743:Phospholipids / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012583:Schwann Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D012584:Sciatic Nerve / Q000166:cytology / Q000378:metabolism*
D004791:Enzyme Inhibitors; D007093:Imidazoles; D048289:Imidazolidines; D010743:Phospholipids; D007294:Inositol; D000449:Aldehyde Reductase; C026411:sorbinil; D005947:Glucose; D001205:Ascorbic Acid