Evidence for diabetes-induced alterations in the sulfation of heparin sulfate intestinal epithelial cells.

35S-heparan sulfate (HS) metabolism by intestinal epithelial cells isolated from streptozotocin-diabetic and control rats was studied. In diabetic cells, a greater amount of 35S-radioactivity was incorporated into HS, however specific radioactivity of this polysaccharide was decreased. Studies into the distribution of sulfate residues in HS after selective deamination of the glucosamine units within the glycosaminoglycan (GAG)-chain, demonstrated that O-sulfate groups are preferentially located in relatively small deamination products: tetrasaccharides and disaccharides. A lower amount of radioactivity related to N-sulfate groups was found in HS from diabetic cells compared to that of control cells demonstrating that, in diabetes, less glucosamine residues within HS chains are subjected to N-sulfation. An increase in the percentage of 35-sulfate and in the percentage amount of uronic acid in tetrasaccharides of HS of diabetic cells indicated that a greater number of tetrasaccharides were generated by deaminative degradation of this HS. Since a decrease in the specific activity of uronic acid in disaccharides as in tetrasaccharides from HS of diabetic cells was observed, it is clear that the degree of O-sulfation of this HS is reduced. It is suggested, that "in vivo" changes in HS metabolism in diabetic intestinal epithelial cells lie in a disturbance in the degree of N- and O-sulfation of disaccharide units within the HS macromolecule.