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Induction of cellualar dysfunction by 3-deoxyglucosome as a mechanism of uremic and diabetic complications

3-脱氧葡萄糖体诱导细胞功能障碍作为尿毒症和糖尿病并发症的机制

基本信息

批准号：
11470216
负责人：
NIWA Toshimitsu
金额：
$ 9.41万
依托单位：
NAGOYA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B).
财政年份：
1999
资助国家：
日本
起止时间：
1999 至 2000
项目状态：
已结题

项目摘要

To determine if 3-deoxyglucosone (3-DG) is involved in the formation of intracellular AGEs, we measured the erythrocyte levels of 3-DG and AGEs such as imidazolone and N^ε-carboxymethyllysine (CML) in hemodialysis (HD) patients with diabetes. Further, to determine if the polyol pathway is involved in the formation of erythrocyte 3-DG and AGEs, an aldose reductase inhibitor (ARI) was administered to these patients. The erythrocyte levels of 3-DG and AGEs are elevated in diabetic HD patients. The administration of ARI reduces the erythrocyte levels of 3-DG and AGEs, especially imidazolone, as well as sorbitol. Thus, 3-DG and AGEs, especially imidazolone, in the erythrocytes are produced mainly via the polyol pathway. ART may prevent diabetic and uremic complications associated with AGEsWe investigated the contribution of high glucose concentration versus the presence of glucose degradation products (GDP) on AGE formation in the peritoneal cavity. Furthermore, the activity of a single chamber bag continuous ambulatory peritoneal dialysis (CAPD) fluid to generate AGE was compared to two double chamber bag PD fluids. During the incubation of HSA with PD-fluids under conditions similar to those of CAPD, only a minor part of AGE formation, measured as CML, imidazolones and fluorescence, derives from high glucose concentration, whereas glucose degradation products, which are formed during heat sterilization are by far the more important glycation precursor. The use of double chamber bags reduces therefore AGE formation considerably. Thus, it can be suggested that also in vivo, double chamber bags can decrease AGE formation in the peritoneal cavity during CAPD.

为了确定3-脱氧葡萄糖醛酮（3-DG）是否参与细胞内AGEs的形成，我们测定了糖尿病血液透析（HD）患者红细胞内3-DG和AGEs如咪唑酮和N^ε-羧甲基赖氨酸（CML）的水平。此外，为了确定多元醇途径是否参与红细胞3-DG和AGEs的形成，对这些患者给予了醛糖还原酶抑制剂（ARI）。糖尿病HD患者红细胞3-DG和AGEs水平升高。ARI的给药降低了红细胞中3-DG和AGEs的水平，尤其是咪唑酮和山梨醇。因此，红细胞中的3-DG和AGEs，特别是咪唑酮，主要通过多元醇途径产生。ART可以预防与AGE相关的糖尿病和尿毒症并发症我们研究了高葡萄糖浓度与葡萄糖降解产物（GDP）对腹膜腔AGE形成的贡献。此外，比较了单腔袋持续性非卧床腹膜透析（CAPD）液与两种双腔袋PD液产生AGE的活性。在与CAPD相似的条件下，HSA与PD液体孵育期间，只有一小部分AGE形成（以CML、咪唑酮和荧光形式测量）来自高葡萄糖浓度，而在热灭菌期间形成的葡萄糖降解产物是迄今为止更重要的糖化前体。因此，双室袋的使用大大减少了AGE的形成。因此，可以表明，在体内，双腔袋也可以减少CAPD期间腹膜腔中AGE的形成。