the polyol pathway as a mechanism for diabetic retinopathy attractive, elusive, and resilient多元醇通路作为糖尿病性视网膜病变的机制有吸引力,令人难以捉摸,而且有弹性.pdfVIP

Hindawi Publishing Corporation Experimental Diabetes Research Volume 2007, Article ID 61038, 10 pages doi:10.1155/2007/61038 Review Article The Polyol Pathway as a Mechanism for Diabetic Retinopathy: Attractive, Elusive, and Resilient Mara Lorenzi Received 26 February 2007; Accepted 24 April 2007 Recommended by Subrata Chakrabarti The polyol pathway is a two-step metabolic pathway in which glucose is reduced to sorbitol, which is then converted to fructose. It is one of the most attractive candidate mechanisms to explain, at least in part, the cellular toxicity of diabetic hyperglycemia because (i) it becomes active when intracellular glucose concentrations are elevated, (ii) the two enzymes are present in human tissues and organs that are sites of diabetic complications, and (iii) the products of the pathway and the altered balance of cofactors generate the types of cellular stress that occur at the sites of diabetic complications. Inhibition (or ablation) of aldose reductase, the first and rate-limiting enzyme in the pathway, reproducibly prevents diabetic retinopathy in diabetic rodent models, but the results of a major clinical trial have been disappointing. Since then, it has become evident that truly informative indicators of polyol pathway activity and/or inhibition are elusive, but are likely to be other than sorbitol levels if meant to predict accurately tissue consequences. The spectrum of abnormalities known to occur in human diabetic retinopathy has enlarged to include glial and neuronal abnormalities, which in experimental animals are mediated by the polyol pathway. The endothelial cells of human retinal vessels have been noted to have aldose reductase. Specific polymorphisms in the promoter region of the aldose reductase gene have been found associated with susceptibilit