Aldose reductase inhibitors and their potential for the treatment of diabetic complications.
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.
Tomlinson
D R
DR
Department of Pharmacology, Queen Mary and Westfield College, University of London, UK.
Stevens
E J
EJ
Diemel
L T
LT
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D048909:Diabetes Complications; D003920:Diabetes Mellitus / Q000201:enzymology / Q000628:therapy*; D003928:Diabetic Nephropathies / Q000188:drug therapy; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D003930:Diabetic Retinopathy / Q000188:drug therapy; D006801:Humans
D000449:Aldehyde Reductase