EFFECTS OF HIGH GLUCOSE-CONCENTRATIONS AND EPALRESTAT ON SORBITOL ANDMYOINOSITOL METABOLISM IN CULTURED RABBIT AORTIC SMOOTH-MUSCLE CELLS

To clarify the relationship between abnormality of sorbitol and/or myo -inositol metabolism caused by hyperglycemia and diabetic macroangiopa thy, we investigated the effects of high glucose concentrations and ep alrestat, an aldose reductase inhibitor, on the metabolism of sorbitol and myo-inositol in cultured rabbit aortic smooth muscle cells. In ce lls incubated in the presence of 30 mM glucose for 72 h, the sorbitol content increased approximately 4.5-fold, and the myo-inositol level d ecreased by 55% compared with control values. Kinetic analysis of high -affinity myo-inositol uptake suggested that smooth muscle cells expos ed to high glucose concentrations exhibited a noncompetitive type of i nhibition characterized by ouabain-sensitive, energy-dependent active transport. Epalrestat blocked glucose-induced changes in sorbitol and myo-inositol metabolism, suggesting that these changes were caused by the accumulation of sorbitol in the cells. These metabolic changes may impair function of smooth muscle cells, contributing to the pathology of diabetic atherosclerosis, especially Monckeberg's calcific medial sclerosis. The use of an aldose reductase inhibitor may prevent these glucose-induced changes.