Tomlinson D R, Stevens E J, Diemel L T
Department of Pharmacology, Queen Mary and Westfield College, University of London, UK.
Trends Pharmacol Sci. 1994 Aug;15(8):293-7. doi: 10.1016/0165-6147(94)90010-8.
Aldose reductase converts glucose to sorbitol, which is further processed to fructose. The enzyme is present in most tissues and its possible physiological role is to produce an electrically neutral, non-diffusible osmolyte in cells exposed to hypertonicity, as typified by the renal medullary cells of the loop of Henlé. The enzyme has a low affinity for glucose, and under normal conditions it processes little substrate. However, in diabetes mellitus, the marked rise in intracellular glucose that occurs in some cells causes marked production of sorbitol. The increased flux and accumulation of sorbitol is damaging to cells and may result in some of the long-term complications of diabetes. In this review, David Tomlinson, Elizabeth Stevens and Lara Diemel discuss the role of aldose reductase and the potential of its inhibitors as therapeutic agents targeted at chronic diabetic complications.
醛糖还原酶将葡萄糖转化为山梨醇，山梨醇再进一步转化为果糖。该酶存在于大多数组织中，其可能的生理作用是在暴露于高渗环境的细胞（如亨氏袢的肾髓质细胞）中产生一种电中性、不可扩散的渗透溶质。该酶对葡萄糖的亲和力较低，在正常情况下处理的底物很少。然而，在糖尿病中，某些细胞内葡萄糖的显著升高会导致山梨醇的大量产生。山梨醇通量增加和积累对细胞具有损害作用，并可能导致糖尿病的一些长期并发症。在这篇综述中，大卫·汤姆林森、伊丽莎白·史蒂文斯和劳拉·迪梅尔讨论了醛糖还原酶的作用及其抑制剂作为针对慢性糖尿病并发症的治疗药物的潜力。
