Rat kidney aldose reductase and aldehyde reductase and polyol production in rat kidney.
Rat kidney aldose reductase and aldehyde reductase and polyol production in rat kidney.
复制标题
大鼠肾醛糖还原酶和醛还原酶以及大鼠肾中多元醇的产生。
作者：
S. Sato
越来越多的证据表明，醛糖还原酶催化的过量葡萄糖还原为山梨糖醇引发某些糖尿病并发症的发作。然而，肾脏含有大量的醛还原酶，另一种NADPH依赖性还原酶。该研究旨在评估这些还原酶对肾脏中糖醇（多元醇）产生的重要性。为了研究将醛糖还原成多元醇的能力，从大鼠肾脏中纯化了醛糖和醛还原酶。用纯化的酶进行的孵育研究清楚地证明了这两种酶的多元醇形成。半乳糖喂养诱导的多元醇积累在髓质和皮质的大鼠肾脏。Al 1576是两种酶的有效抑制剂，减少了皮质和髓质中的多元醇积累，而选择性抑制剂Ponalrestat或FK 366在髓质中的抑制作用大于皮质。这些结果表明，肾脏多元醇可能产生的醛糖和醛还原酶和醛还原酶有助于多元醇的生产在肾皮质，糖尿病相关的肾脏病变的主要网站。
Mounting evidence indicates that aldose reductase catalyzed reduction of excess glucose to sorbitol initiates the onset of certain diabetic complications. However, the kidney contains a large amount of aldehyde reductase, another NADPH-dependent reductase. The study was designed to assess the importance of these reductases to sugar alcohol (polyol) production in the kidney. To study the ability to reduce aldoses to polyols, both aldose and aldehyde reductases were purified from rat kidneys. Incubation studies with purified enzymes clearly demonstrated the polyol formation by both enzymes. Galactose feeding induced polyol accumulation in both medulla and cortex of the rat kidney. Al 1576, a potent inhibitor of both enzymes, reduced this polyol accumulation in both cortex and medulla, while the selective inhibitors Ponalrestat or FK 366 resulted in greater inhibition in medulla than cortex. These results suggest that kidney polyols may be generated by both aldose and aldehyde reductases and that aldehyde reductase contributes to polyol production in the kidney cortex, the predominant site of diabetes-linked kidney lesions.