Sakakibara F, Hotta N, Koh N, Sakamoto N
Third Department of Internal Medicine, Nagoya University School of Medicine, Japan.
Diabetes. 1993 Nov;42(11):1594-600. doi: 10.2337/diab.42.11.1594.
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.
为了阐明高血糖导致的山梨醇和/或肌醇代谢异常与糖尿病大血管病变之间的关系，我们研究了高糖浓度和醛糖还原酶抑制剂依帕司他对培养的兔主动脉平滑肌细胞中山梨醇和肌醇代谢的影响。在30 mM葡萄糖存在下孵育72小时的细胞中，山梨醇含量增加了约4.5倍，与对照值相比，肌醇水平降低了55%。对高亲和力肌醇摄取的动力学分析表明，暴露于高糖浓度的平滑肌细胞表现出一种非竞争性抑制类型，其特征为对哇巴因敏感、能量依赖的主动转运。依帕司他阻断了葡萄糖诱导的山梨醇和肌醇代谢变化，表明这些变化是由细胞中山梨醇的积累引起的。这些代谢变化可能会损害平滑肌细胞的功能，导致糖尿病性动脉粥样硬化的病理过程，尤其是门克伯格氏中层钙化性硬化。使用醛糖还原酶抑制剂可能会阻止这些由葡萄糖诱导的变化。
