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

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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.