Urocortin ameliorates diabetic nephropathy in obese db /db mice
Urocortin ameliorates diabetic nephropathy in obese db/db mice出 版 物：《南京医科大学学报(自然科学版)》 (Journal of Nanjing Medical University(Natural Sciences))
年 卷 期：2008年第10期
页 面：1311-1311页
学科分类：1002[医学-临床医学] 100210[医学-外科学(含：普外、骨外、泌尿外、胸心外、神外、整形、烧伤、野战外)] 10[医学]
主 题：urocortin diabetic nephropathy extra cellular matrix glycation end-products tissue growth-factor mesangial cells polyol pathway iv collagen in-vivo rat expression insulin complications
摘 要：Background and purpose: Hyperglycaemia induces overproduction of mitochondrial reactive oxygen species (ROS) in endothelial cells, which is believed to be a major molecular mechanism underlying complications of diabetes, including diabetic nephropathy. Impairment of endothelium-dependent vasodilatation is found in type 2 diabetes. Urocortin is a 40 amino-acid peptide related to the corticotrophin-releasing factor (CRF) family, which suppresses production of ROS in endothelial cells and sustains endothelium-dependent relaxations of rat coronary artery. However, it is not clear if urocortin has any effect on diabetic nephropathy. Experimental approach: Possible mechanisms underlying the effects of urocortin on diabetic nephropathy were investigated in db/db mice and cultured rat mesangial cells. Key results: Urocortin decreased body weight, plasma levels of advanced glycation end-prod ucts, blood urea nitrogen and creatinine levels. However, food intake, plasma insulin and glucose levels remained unaffected. Superoxide dismutase activity was increased markedly, whereas malonaldehyde levels in kidney homogenate and sorbitol concentrations in red blood cells were decreased significantly in urocortin-treated mice. Urocortin significantly decreased glomerular extracellular matrix expansion and accumulation in kidney. Moreover, urocortin inhibited the overexpression of transforming growth factor-beta 1 and connective tissue growth factor in rat mesangial cells induced by 25 mM glucose. All the effects of urocortin, except sorbitol accumulation, were abolished by the non-selective CRF receptor blocker, astressin. Conclusion and implications: Urocortin could significantly ameliorate diabetic nephropathy and this effect was mediated via the
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