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.
Lipids extracted from erythrocyte membranes were analyzed by gas chromatographic mass spectrometry.7-ketocholestadiene (KD) was identified in diabetics as a product of cholesterol peroxidation, but not identified in healthy subjects. In addition, a significant correlation was found between HbA1c values and relative peak areas of KD and cholesterol in the chromatograms. These results suggest that 1) lipid peroxidation occurs not only to unsaturated fatty acids but to cholesterol in erythrocyte membranes, and 2) KD from erythrocyte membranes is suitable as marker of lipid peroxidation and is a useful indicator of peroxidative damage in diabetics.