In this study, we examined the hypothesis whether exogenous administration of L-lysine in drinking water would reduce nonenzymatic glycation of glomerular basement membrane (GBM) collagen and thus albuminuria in streptozotocin-diabetic rats. The rationale is that the administered lysine would combine with the circulating glucose and make it unavailable to react with Ε-amino groups of lysine of various proteins in these diabetic rats. Lysine (0.1%) was given to diabetic rats 7 days (early treatment) or 90 days (late treatment) after induction of hyperglycemia. The treatment was continued for 60 days. Diabetic rats had significantly higher glucose, glycosylated HbA1, kidney weight, nonenzymatic glycation of GBM collagen, albuminuria, and systolic blood pressure than normal rats. Early treatment with lysine prevented the rise in glycosylated HbA1 (normal 6.98 ± 0.71% vs. diabetic – early treatment – 7.78 ± 1.50%; p = NS), reduced glycosylation of GBM collagen by 86%, and significantly improved albuminuria. There was no significant effect on plasma glucose and systolic blood pressure. However, late treatment reduced the glycosylation of GBM collagen by 46% with a significant improvement in albuminuria. Plasma creatinine levels were not different between normal and untreated diabetic or lysine-treated diabetic rats; however, the creatinine clearance was significantly higher in all groups of diabetic rats (normal 0.45 ± 0.09 vs. diabetic 2.02 ± 0.39 ml/min; p < 0.001). The data suggest that early rather than late treatment is more beneficial in reducing nonenzymatic glycation of collagen, although both treatments significantly reduced albuminuria. There was no nephrotoxicity as assessed by plasma creatinine levels or creatinine clearances. These beneficial effects occurred independent of changes either in blood pressure or plasma insulin concentration.

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