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Development of a method for early diagnosis of diabetic of complications by detecting glycation reaction intermediates.

开发通过检测糖化反应中间体来早期诊断糖尿病并发症的方法。

基本信息

批准号：
09557017
负责人：
FUJII Junichi
金额：
$ 7.94万
依托单位：
Osaka University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 1998
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-09557017/
关键词：
Diabetic complicatrions Glycation Crystallin Glucose Fructose Polyol pathway Cataract

项目摘要

Glycation occurs during normal aging and at accelerated rates in diabetes and is involved in structural and functional alterations of proteins and other cellular components. In terms of diabetic complications, the glycation hypothesis and the poiyol pathway hypothesis are usually discussed independently. An antibody was raised against fructated lysine in proteins by immunizing fructated lysine-conjugated ovalbumin in rabbits. The affinity purified antibody specifically recognized proteins incubated with fructose, but not with glucose. When bovine serum albumin was incubated with various concentrations of fructose, the reactivity of thee antibody increased in a dose- and time-dependent manner. When soluble proteins prepared from either normal or streptozotocin-induced diabetic rat eyes were analyzed by ELISA using this antibody, an increase in the reactive components was observed as a function of aging as well as under diabetic conditions. Immunoblot analysis showed that lens crystallin reacted highly with this antibody. Since fructose is largely biosynthesized through the polyol pathway, which is enhanced under diabetic conditions and lens is known to have a high activity of this pathway, this antibody is capable of recognizing fructated proteins in viva. Thus this antibody represents a potentially useful tool for investigating two major issues which appear to be involved in diabetic complications, namely, the glycation reaction and the polyol pathway.

糖基化发生在正常衰老过程中，并在糖尿病中以加速的速率发生，并且涉及蛋白质和其他细胞组分的结构和功能改变。在糖尿病并发症方面，糖基化假说和多元醇途径假说通常被独立讨论。用果糖赖氨酸偶联卵清蛋白免疫家兔，制备了抗蛋白质中果糖赖氨酸的抗体。亲和纯化的抗体特异性识别与果糖孵育的蛋白质，但不与葡萄糖孵育。当牛血清白蛋白与不同浓度的果糖孵育时，抗体的反应性以剂量和时间依赖性的方式增加。当使用该抗体通过ELISA分析从正常或链脲佐菌素诱导的糖尿病大鼠眼睛制备的可溶性蛋白质时，观察到反应性组分的增加作为衰老的函数以及在糖尿病条件下。免疫印迹分析表明，透镜晶体蛋白与该抗体高度反应。由于果糖主要通过在糖尿病条件下增强的多元醇途径生物合成，并且已知透镜具有该途径的高活性，因此该抗体能够在体内识别果糖蛋白。因此，这种抗体代表了一个潜在的有用的工具，用于调查似乎参与糖尿病并发症，即糖化反应和多元醇途径的两个主要问题。