Interactions between advanced glycation and oxidative stress in diabetic renal and cardiac complications

肾脏和心脏病是糖尿病的严重并发症。这些并发症是西方世界残疾和过早死亡的主要原因。我们小组和其他人的研究表明，糖尿病并发症似乎是许多不同过程的结果。这些途径包括蛋白质如胶原蛋白和糖之间不可逆相互作用的糖依赖性途径，称为晚期糖化。晚期糖基化的过程改变了身体更新这些蛋白质的能力，从而导致衰老过程的加速。事实上，据估计，这一过程在糖尿病中的发生速度几乎快50倍。这些粘性复合物在组织中积累，导致正常组织结构的破坏。我们的团队有一种药物，可以像剪刀一样切断蛋白质上的粘性糖，使其翻转。不幸的是，这并不能修复所有的损坏。这些AGE分子参与许多其他有害过程，包括产生有毒的氧衍生分子，这些分子是糖尿病的有害副产品。虽然这些氧“自由基”与心脏病发作和中风有关，但它们的来源在糖尿病中仍然是一个谜。以前，去除这些分子的唯一方法是用维生素E等抗氧化剂将其清除。抗氧化剂工作缓慢，所以在它们“解毒”这些氧自由基之前已经造成了一些损害。我们建议使用药物组合，看看我们是否可以在实验性糖尿病中实现更有效的保护。这可能为糖尿病肾病和心脏病的治疗提供新的治疗方法。

Kidney and heart disease are serious complications of diabetes. These complications are the major cause of disability and premature death in the western world. Studies from our group and others have shown that diabetic complications appear to be a consequence of a number of different processes. These pathways include a sugar dependent pathway of irreversible interactions between proteins such as collagen and sugar known as advanced glycation. The process of advanced glycation alters the body's ability to renew these protein, hence causing accelration of the ageing process. In fact, it is estimated that this process occurs almost fifty times faster in diabetes. These sticky complexes accumulate in tissues causing disruption ot the normal tissue structure. Our group has a drug which can act as scissors and cut the sticky sugar off the proteins allowing it to be turned over. Unfortunately this does not fix all of the damage. These AGE molecules are involved in a number of other harmful processes including the production of toxic oxygen derived molecules which are harmful byproducts of diabetes. While these oxygen 'radicals' have been implicated in heart attack and stroke their source has remained a mystery in diabetes. Previously, the only way to remove these molecules was to mop them up with antioxidants such as Vitamin E. Antioxidants work slowly and so some damage is already done before they 'detoxify' these oxygen radicals. We propose to use combinations of medicines to see if we can achieve more effective protection against these processes in experimental diabetes. This may provide new therapies for threatment of kidney and heart disease in diabetes.