Nonenzymatic glycosylation of peripheral nerve protein in diabetes mellitus.

A new affinity chromatography system that selectively retains glycosylated amino acids has been utilized to determine the amount of nonenzymatic glycosylation present in peripheral nerve from diabetic and control rats and dogs. The mean value for glycosylated amino acids in diabetic rats was 2.8 times greater than the mean value in normal rats (P less than 0.001). In diabetic dogs, mean values were 2.15 times greater than normal values (P less than 0.05). Amino acid analysis of reduced, glycosylated amino acids previously isolated by affinity chromatography showed that glycosylated lysine and its hydrolysis rearrangement products were the major borohydride-reducible adduct present. In addition, another glycosylated product was noted to be present in major proportions. This radioactive product did not chromatograph with any of the available glycosylated amino acid standards. The finding that diabetes results in a nearly 3-fold increase of peripheral nerve glycosylation is consistent with a number of previous investigations in which glycosylation was measured in hemoglobin, serum albumin, and urinary amino acids and peptides from diabetics and normals. The results reported here provide evidence that increased nonenzymatic glycosylation is occurring in a tissue where physiological, morphological, and clinical degeneration characteristically develop as a result of diabetes mellitus.