The Effect of Aminoguanidine and Insulin on the Development of Insulitis and the Expression of Inducible Nitric Oxide Synthase in Multiple Low Dose Streptozotocin-induced Diabetic Mice

ABSTRACT

In this study the effect of insulin and aminoguanidine on the expression of iNOS and the development of insulitis in the multiple low dose streptozotocin (SZ) induced diabetic (LDSD) mice was evaluated. Eighty mice (Charles-River CD-1 mice) were divided into four groups. Group I received SZ for five days. Group II received SZ for five days and was followed by insulin treatment. Group III received SZ for five days and was followed by aminoguanidine treatment. Group IV was normal control group. The blood glucose level and body weight were measured weekly. On the 35th day, pancreat ic sections were observed to evaluate the frequency and the severity of insulitis in addition to the immunohistochemical expression of iNOS in the pancreatic islets. Blood glucose levels of group IV were significantly lower than other experimental groups on the 21st, 28th, and 35th day. The difference in blood glucose levels was not statistically significant. Incidence of the insulitis was lower in group II than in groups I and III. The severity of insulitis correlated with the increase in blood glucose level only in group II. The expression of iNOS was more pronounced in group I than in groups II and III. Aminoguanidine did not inhibit development of the insulitis but decreased expression of iNOS in the pancreatic islets. Therefore it is speculated that iNOS production is one of the factors and other pathogenetic mechanisms might be involved in the development of insulitis.