Bylander J E, Sens D A
Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston 29425.
Diabetes. 1990 Aug;39(8):949-54. doi: 10.2337/diab.39.8.949.
The human proximal tubule (HPT) is the characteristic site within the kidney that mediates absorption of glucose. This study was designed to determine whether cultured HPT cells would respond to a hyperglycemic environment through activation of the polyol pathway. The results of this study clearly indicate that exposure of the HPT cells to an extracellular glucose concentration greater than or equal to 11 mM results in substantial intracellular accumulation of sorbitol. This accumulation is inhibited by approximately 70% by treatment with 100 microM sorbinil. When cells growing 24 h on 27.5 mM glucose were changed to medium containing 5.5 mM glucose, sorbitol concentration returned to the control level within 12 h. The activity of aldose reductase was increased by a factor of 1.6 by exposure to elevated glucose concentrations, and the relative reactivity of the enzyme with glucose as substrate was approximately 0.1 compared with that of glyceraldehyde as substrate. Together, these results indicate that cultured cells derived from the HPT undergo activation of the polyol pathway when exposed to a hyperglycemic environment.
人近端小管（HPT）是肾脏内介导葡萄糖吸收的特征性部位。本研究旨在确定培养的HPT细胞是否会通过多元醇途径的激活对高血糖环境作出反应。本研究结果清楚地表明，将HPT细胞暴露于细胞外葡萄糖浓度大于或等于11 mM的环境中会导致山梨醇在细胞内大量积累。用100 microM索比尼尔处理可使这种积累减少约70%。当在27.5 mM葡萄糖上生长24小时的细胞更换为含有5.5 mM葡萄糖的培养基时，山梨醇浓度在12小时内恢复到对照水平。通过暴露于升高的葡萄糖浓度，醛糖还原酶的活性增加了1.6倍，与以甘油醛为底物相比，该酶以葡萄糖为底物的相对反应性约为0.1。这些结果共同表明，源自HPT的培养细胞在暴露于高血糖环境时会经历多元醇途径的激活。
