Hypoglycemic effect of intestinally administered monosaccharide-modified insulin derivatives in rats.

The effect of the modification of insulin (INS) with p-succinylamidophenyl (SA)-alpha-D-glucopyranoside (SAPG), SA-alpha-D-mannopyranoside and SA-alpha-L-arabinopyranoside on the enzymatic degradation and the hypoglycemic effect in rats was studied. When SAPG-INS was administered intraintestinally in the absence of bile and pancreatic juice, blood glucose level decreased to 56% of initial value. Other monosaccharide derivatives were less effective than SAPG-INS. The digestion of monosaccharide derivatives by pepsin and chymotrypsin indicated that the resistance of insulin to enzymatic degradation was increased by its modification with monosaccharide. One possibility for the hypoglycemic effect of SAPG-INS could be the increased resistance of insulin to enzymatic degradation as a result of its modification with monosaccharide.