GLYCATION OF PROTEIN IN DIABETES

糖尿病慢性高血糖的化学后果之一是 糖化（非酶糖化）的身体负担增加 proteins. 糖基化被认为是一系列复杂的糖基化反应的第一步。 葡萄糖和蛋白质之间的美拉德或布朗宁反应， 在体外，对蛋白质的变性、交联和不溶性有影响。 假设这些相同的反应也可能发生在体内， 蛋白质结构的改变可能会加速 糖尿病和正常衰老过程中的病理变化。 持续增 眼、肾和脉管系统慢性并发症的发展， 糖尿病与增加的交联和不溶解有关， 透镜、基底膜和结缔组织蛋白。 伴随 这些长寿命细胞的糖基化、布朗宁和荧光增加 细胞外蛋白表明美拉德反应可能参与 在这些过程中。 这项研究建议的主要目的是继续研究 蛋白质的糖基化及糖基化蛋白的布朗宁反应的作用 糖尿病和衰老的病理生理学中的蛋白质。 具体目标 包括：（1）美拉德产物结构表征 模拟氨基酸-葡萄糖布朗宁体系的研究; 指导蛋白质糖基化的体内外特异性; (3)荧光染料的结构和形成机理的研究 在模型的Maillard反应中产生的交联化合物 体外蛋白质;和（4）开发和应用的方法， 美拉德反应产物及其体内催化剂的测量。 我们希望能更好地了解梅拉德 在正常和病理条件下发生的体内反应将 增加我们对它们在糖尿病并发症中的作用的理解。 这些知识应该为设计和评估提供更好的基础 糖尿病的治疗方法。

One of the chemical consequences of chronic hyperglycemia in diabetes is an increased body burden of glycated (nonenzymatically glycosylated) proteins. Glycation is recognized as the first step in a complex series of Maillard or browning reactions between glucose and protein which lead, in vitro, to the denaturation, crosslinking and insolubilization of protein. It is hypothesized that these same reactions may also occur in vivo, and that the alterations in protein structure may precipitate the development of pathology in tissues in diabetes and during normal aging. Indeed, the development of chronic complications in the eye, kidney and vasculature in diabetes is associated with increased crosslinking ahd insolubilization of lens, basement membrane and connective tissue proteins. Concomitant increases in glycation, browning and fluorescence of these long-lived extracellular proteins suggest that the Maillard reaction may be involved in these processes. The major objective of this research proposal is to continue studies on the glycation of protein and the role of the browning reaction of glycated proteins in the pathophysiology of diabetes and aging. Specific aims include: (1) structural characterization of Maillard products formed in model amino acid-glucose browning systems; (2) studies of factors which direct the specificity of glycation of protein in vitro and in vivo; (3)\studies on the structure and mechanism of formation of fluorescent and crosslinking compounds generated during Maillard reactions of model proteins in vitro; and (4) development and application of methods for measurement of Maillard reaction products and their catabolites in vivo. We expect that a better understanding of the extent to which Maillard reactions occur in vivo under normal and pathological conditions will increase our understanding of their role in the complications of diabetes. This knowledge should provide a better basis for the design and evaluation of therapeutic approaches to the management of diabetes.