Effect of streptozotocin-induced diabetes on the structure of heparan sulfate from rat kidneys.

The effect of streptozotocin-induced diabetes on the structure of heparan sulfate (HS) prepared from rat kidney glycosaminoglycans (GAG) was evaluated. GAG were isolated and purified from the kidneys of diabetic and age-matched control rats by standard procedures. HS was prepared from GAG by digestion with chondroitinase ABC and precipitation with cetylpyridinium chloride. The tissue dry weight of diabetic kidneys was greater than that of the controls. The amounts of protein and DNA per tissue dry weight were decreased in the diabetic group, while GAG and hydroxyproline remained unchanged. The above information indicates that the extracellular components are increased in diabetes. There was no significant difference in the amount of HS to tissue dry weight between the diabetic and control groups. When the molecular weight of the HS from both groups was compared by Sephacryl S-300 HR column chromatography, the HS peak for the diabetic kidney indicated a slightly higher molecular weight and the base of the peak was broader than that for the controls. A reduction in N-sulfate residues was observed in Sephadex G-50 profiles after nitrous acid degradation of the HS. The ratio of glucuronic acid to its epimer, iduronic acid, in diabetic kidney HS was slightly lower than that in the controls. This indicates that diabetes may influence the carbohydrate chain structure of the HS in the kidney. Quantitative and qualitative changes in the kidney HS may contribute to the symptoms associated with diabetic nephropathy.