Abstract
Recent studies have demonstrated that free radicals and/or cytokines secreted by macrophages are involved in autoimmune islet destruction and that several antioxidants prevent the development of type I diabetes in animal models. CS-045 is a newly developed oral antidiabetic agent.This agent lowers plasma glucose in NIDDM by increasing insulin sensitivity and also displays strong anitioxidative effects. In this study, the effect of CS-045 as an antioxidant on the development of autoimmune diabetes was studied.NOD female mice were given either a standard or 0.2%CS-045-containing diet at 5 weeks of age. Cyclophosphamide (150mg/kg) was injected intraperitoneally at 10 weeks of age. After cyclophosphamide injection, animals were screened for diabetes for 4 weeks and sacrificed at 14 weeks of age. During the screening period, 14 of the 24 control mice became diabetic, whereas, only one mouse fed CS-045 (1/15) developed diabetes. Although, there was no difference percentage of between groups in insulitis (48.9±17.1vs62.2±18.7%, us), islet β cell mass was well preserved in CS-045 treated mice in comparison with control mice (0.26±0.17vs0.06±0.01%, P<0.01). These findings indicate that CS-045 retained more islet β cells and reduced the incidence of diabetes in NOD mice.
