INHIBITION OF DIABETES-ASSOCIATED COMPLICATIONS BY NUCLEOPHILIC COMPOUNDS

Mono- and diaminoguanidine inhibited ambient glucose-induced glycosylated end product formation of albumin and collagen I-125-labeled albumin covalent binding in vitro. Diaminoguanidine was a stronger inhibitor than monoaminoguanidine. These compounds also inhibited rat eye lens aldose reductase activity in vitro noncompetitively with respect to NADPH with K(i) = 30.6 mM for monoaminoguanidine and K(i) = 12.5 mM for diaminoguanidine. When administered daily for 98 days at a dose of 25 mg/kg body wt i.p. both compounds lowered eye lens sorbitol and aldose reductase activity in normoglycemic and alloxan-induced diabetic rats. Again, diaminoguanidine was a better inhibitor. Daily long-term administration of mono- and diaminoguanidine (25 mg/kg body wt i.p.) inhibited and prevented experimental diabetes-induced lens opacity in rats, respectively. It appears that diaminoguanidine has a better therapeutic potential in controlling diabetic complications.