Circulating low -molecular weight AGEs in the development and progression of diabetic complications

糖尿病患者体内的高糖分会导致心脏、眼睛和肾脏等多个器官受损。这些高糖通过一系列机制造成损害，其中之一是由蛋白质和葡萄糖之间不可逆转的反应形成的高级糖基化终产物或AGEs的形成。这种反应导致AGE修饰分子的形状和功能发生变化，从而逐渐导致器官损伤。AGEs还结合并激活促进组织损伤和疤痕形成的特定受体。在葡萄糖浓度较高的地方，AGE积累得更快。这就是为什么血糖控制良好的患者比血糖控制不好的患者表现更好的原因之一。阻止AGEs的形成能够预防糖尿病动物的肾脏损害，这一事实说明了这一AGE途径的重要性。此外，在缺乏高糖的情况下，暴露于AGEs会导致糖尿病样变化。我们的实验室在研究高级糖基化和阻止这一过程的方法方面处于世界领先地位。这项拟议的研究将调查实验动物和糖尿病患者的循环AGEs水平，并将它们与糖尿病并发症的发生和进展联系起来。

High levels of sugars seen in patients with diabetes leads to damage of many organs including the heart, the eyes and the kidneys. These high sugars cause damage through a number of mechanisms, one being the formation of advanced glycation end products or AGEs, formed by the irreversible reaction between proteins and glucose. This reaction leads to a change in the shape and function of AGE-modified molecules that progressively contributes to organ damage. AGEs also bind and activate specific receptors that promote the damage and scarring of tissue. Where the glucose concentration is high, AGEs accumulate much more quickly. This is one reason why patients with good sugar control do better than those who are unable to control their blood sugars. The importance of this AGE pathway is illustrated by the fact that blocking the formation of AGEs is able to prevent kidney damage in animals with diabetes. In addition, exposure to AGEs can cause diabetes-like changes in the absence of high sugars. Our laboratory is a world leader in the study of the advanced glycation and methods blocking this process. The research proposed will investigate circulating levels of AGEs in experimental animals and patients with diabetes, and correlate them with the development and progression of complications of diabetes