期刊
PROTEIN AND PEPTIDE LETTERS
卷 24, 期 1, 页码 71-77出版社
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929866523666161128153548
关键词
Diabetic nephropathy; aldose reductase; polyol pathway; protein kinase C; sorbitol; oxidative stress; advanced glycation end products
资金
- Office of Academic Research, Qatar University [QUST-CPH-SPR-12/13-4, QUST-CPH-FALL-13/14-5, QUST-CPH-SPR-13/14-7, QUST-CPH-FALL-14/15-6, QUST-CPH-SPR-14/15-15]
Diabetic nephropathy (DN) is one of the most serious microvascular complications of diabetes mellitus and the leading cause of end stage renal disease. One of the key pathways activated in DN is the polyol pathway, in which glucose is converted to sorbitol (a relatively non metabolizable sugar) by the enzyme aldose reductase (AR). Shunting of glucose into this pathway causes disruption to glucose metabolism and subsequently damages the tissues via increased oxidative stress, protein kinase c activation and production of advanced glycation end products (AGE) in the kidney. This review aims to provide a comprehensive overview of the AR enzyme structure, substrate specificity and topology in normal physiology; to elaborate on the deleterious effects of AR activation in DN; and to summarize the potential therapeutic benefits and major challenges associated with AR inhibition in patients with DN.
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