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

为探讨3-脱氧葡萄糖苷(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的水平，包括咪唑酮和N-ε-羧甲基赖氨酸(CML)。此外，为了确定多元醇途径是否参与了红细胞3-DG和AGEs的形成，对这些患者应用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。服用ARI可降低红细胞内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)在腹膜腔内AGE形成中的作用。此外，还比较了单腔袋持续非卧床腹膜透析液(CAPD液)和两种双腔袋腹膜透析液(CAPD液)产生AGE的活性。在与CAPD相似的条件下，HSA与Pd液孵育过程中，只有一小部分AGE的形成(CML、咪唑酮和荧光)来自高葡萄糖浓度，而在热灭菌过程中形成的葡萄糖降解产物是迄今为止更重要的糖基化前体。因此，双腔袋的使用大大减少了老化的形成。因此，可以认为，在体内，双腔袋也可以减少CAPD期间腹膜腔内AGE的形成。

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.