Potential benefit of inhibitors of advanced glycation end products in the progression of type II diabetes: A study with aminoguanidine in C57/BLKsJ diabetic mice

Prolonged hyperglycemia in type II diabetic patients is linked both with di abetic complications and with further impairment of glucose homeostasis. po ssibly due to glucose toxicity of the beta cell. While the connection betwe en the accumulation of extracellular advanced glycation end products (AGEs) and the development of complications is well established, it has only rece ntly been suggested that intracellular glycation may be equally adverse and could be involved in the pathogenesis of glucose toxicity in vitro. Aminog uanidine is a recognized inhibitor of the formation of both extracellular a nd intracellular AGEs. In this study, we show that the development of diabe tes, measured by increased water intake and concomitant midday blood glucos e levels in type II genetically diabetic mice, is reduced by treatment with aminoguanidine at a dosage of 500 mg/kg/d for 12 weeks in the diet. In add ition, at the end of the study, aminoguanidine reduced the decline in serum and pancreatic insulin levels and the degree of pancreatic islet morpholog ical degeneration, all of which are associated with pancreatic insufficienc y following prolonged hyperglycemia in this animal model. These results sug gest that AGEs may be involved in the aggravation of type II diabetes in vi vo and aminoguanidine may be beneficial in its treatment. Copyright (C) 199 8 by W.B. Saunders Company.