Effects of high glucose concentrations and epalrestat on sorbitol and myo-inositol 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 macroangiopathy, we investigated the effects of high glucose concentrations and epalrestat, an aldose reductase inhibitor, on the metabolism of sorbitol and myo-inositol in cultured rabbit aortic smooth muscle cells. In cells incubated in the presence of 30 mM glucose for 72 h, the sorbitol content increased approximately 4.5-fold, and the myo-inositol level decreased by 55% compared with control values. Kinetic analysis of high-affinity myo-inositol uptake suggested that smooth muscle cells exposed to high glucose concentrations exhibited a noncompetitive type of inhibition 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 Mönckeberg's calcific medial sclerosis. The use of an aldose reductase inhibitor may prevent these glucose-induced changes.
Sakakibara
F
F
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Hotta
N
N
Koh
N
N
Sakamoto
N
N
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors; D000818:Animals; D001011:Aorta / Q000166:cytology; D001693:Biological Transport, Active / Q000502:physiology; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005632:Fructose / Q000494:pharmacology; D005934:Glucagon / Q000494:pharmacology; D005947:Glucose / Q000494:pharmacology*; D007294:Inositol / Q000032:analysis / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D009131:Muscle, Smooth, Vascular / Q000737:chemistry / Q000166:cytology* / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D011817:Rabbits; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D012964:Sodium / Q000494:pharmacology; D013012:Sorbitol / Q000032:analysis / Q000378:metabolism*; D053778:Thiazolidines
D007328:Insulin; D053778:Thiazolidines; D005632:Fructose; D003571:Cytochalasin B; C038131:epalrestat; D007294:Inositol; D013012:Sorbitol; D010042:Ouabain; D012236:Rhodanine; D005934:Glucagon; D012964:Sodium; D000449:Aldehyde Reductase; D005947:Glucose