Probucol partially prevents development of diabetes in NOD mice

We examined the hypothesis that the hypocholesterolemic agent, probucol (4,4'-(isopropylidenedithiol) bis (2,6-di-tert-butyl-phenol)), can attenuate development of hyperglycemia in NOD mice. The female NOD mice were fed 1% probucol containing (PROB) or standard diet (CONT) from 5 weeks of age. Development of hyperglycemia was checked by urine glucose levels using stick paper for 35 weeks. At 40 weeks of age, all animals were sacrificed and plasma glucose and serum immunoreactive insulin (IRI) levels were measured. At 40 weeks of age, 80.0% of mice showed hyperglycemia (greater than 200 mg/dl) or death in CONT group. In contrast, only 46.7% showed hyperglycemia in PROB group. Plasma glucose levels of PROB group tended to be lower than those of CONT group. The percentage of Thy 1.2-positive splenocytes were significantly lower in PROB group than that in CONT group. In addition, the splenocytes positive with Lyt. 2 were also reduced by probucol administration. These data suggest that probucol can partially prevent development of diabetes in NOD mice. It is possible that the observed changes of T-cell subsets in the spleen may be involved in the prevention of diabetes.