rhodanine and fructose-3-phosphate

Fructose 3-phosphate and sorbitol 3-phosphate are novel metabolites that have been shown to associate with the polyol pathway in animal experiments. Fructose 3-phosphate is of particular interest because of its potent glycation capability as compared with other glycolytic intermediates, e.g., fructose. We observed the effects of treatment with epalrestat, an aldose reductase inhibitor, on their concentrations in erythrocytes from diabetic patients. The levels of both metabolites were significantly higher in diabetic patients than in non-diabetic subjects. A group of patients who had been treated with epalrestat showed significantly lower levels of both metabolites as compared with those untreated. A treatment of three patients with epalrestat for one month resulted in obvious decreases in their concentrations. The results suggest a possible explanation for the preventive effect of an aldose reductase inhibitor on nonenzymatic glycation.

Topics: Adult; Aldehyde Reductase; Blood Glucose; Diabetes Mellitus, Type 2; Erythrocytes; Fasting; Female; Fructosephosphates; Hexosephosphates; Humans; Magnetic Resonance Spectroscopy; Male; Middle Aged; Phosphorus Isotopes; Reference Values; Rhodanine; Thiazolidines

To investigate the effect of fructose ingestion on sorbitol and fructose 3-phosphate (F3P) in erythrocytes, we administered 50 g fructose with and without treatment with an aldose reductase inhibitor, epalrestat, to seven healthy, normal-glucose-tolerant, male volunteers aged 20-43 years. The same subjects were given 50 g glucose on another day. The sorbitol and F3P contents in their erythrocytes increased significantly, reaching peak levels at 60 min and 180 min, respectively, following fructose in gestion. On the other hand, glucose ingestion did not cause any statistically significant change in sorbitol content in their erythrocytes, although it significantly elevated their F3P content. Treatment with epalrestat had no significant effect on incremental changes in erythrocyte sorbitol and F3P content following fructose ingestion. This suggests that oral fructose may be converted directly to sorbitol and F3P in erythrocytes instead of being converted via glucose. Thus, the dietary intake of fructose may affect the concentrations of sorbitol and F3P in erythrocytes in normal men.

Topics: Adult; Aldehyde Reductase; Erythrocytes; Fructose; Fructosephosphates; Glucose; Humans; Male; Rhodanine; Sorbitol; Thiazolidines; Time Factors

In order to confirm the link between nonenzymatic glycation and the polyol pathway, we observed the effect of treatment with epalrestat (Ep), an aldose reductase inhibitor, on the concentration of advanced glycation end-products (AGEs) in erythrocytes from diabetic patients. We also examined the effect of the drug on erythrocyte fructose 3-phosphate (F3P), a novel metabolite that has been reported to relate to the polyol pathway, and ascertained the glycation capability of F3P and its possible breakdown product, 3-deoxyglucosone (3DG), by incubating the metabolites with bovine serum albumin (BSA). Incubation of BSA with F3P or 3DG resulted in a greater production of AGEs in comparison with the incubation with glucose or fructose. F3P was significantly increased in erythrocytes from diabetic patients compared with those from nondiabetic individuals and was lower in patients who had been treated with Ep than in those who were free from the compound. A treatment of patients with Ep for 1 month resulted in a significant decrease in F3P. Erythrocyte AGEs were significantly elevated in diabetic patients compared with nondiabetic individuals and tended to be lower in patients taking Ep than in those without Ep. Administration of Ep for 2 months decreased AGEs. These results show that the polyol pathway is likely to play a substantial role in the nonenzymatic glycation of proteins and the suppression of E3P as well as AGEs by an aldose reductase inhibitor may explain in part the preventive effect of the drug on diabetic complications.

Topics: Aldehyde Reductase; Animals; Cattle; Deoxyglucose; Diabetes Mellitus, Type 2; Enzyme Inhibitors; Erythrocytes; Fructosephosphates; Glycation End Products, Advanced; Glycosylation; Humans; In Vitro Techniques; Polymers; Rhodanine; Serum Albumin, Bovine; Thiazolidines