Accelerated onset of albuminuria in diabetic rats preimmunized with glucosylated rat serum albumin

Young adult rats were immunized with either in vitro glucosylated or unmodified rat serum albumin (RSA) followed by induction of the diabetic state. At various times after streptozotocin administration, sera were evaluated for specific antibody response using the enzyme-linked immunosorbent assay while urine was monitored for the presence of albumin by radial immunodiffusion. The data indicate that glucosylated RSA is capable of eliciting the production of antibodies, but unmodified RSA is not. The specificity of the generated antibodies appears to be directed toward the glucitollysine residues of the modified albumin. Preimmunization of rats with glucosylated RSA followed by induction of diabetes causes a rapid decline in specific antibody titers and greatly enhances the rate of progression to albuminuria. These results demonstrate that in vitro and in vivo glucosylation of an endogenous protein provide products with identical antigenicity. They also suggest an animal model for the study of diabetic autoimmunity involving glucosylated endogenous proteins.