Disulfiram Reduces Elevated Blood Glucose Levels in Otsuka Long-Evans Tokushima Fatty (OLETF) Rats, a Model of Type 2 Diabetes

The Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an established model of human type 2 diabetes mellitus. We investigated the effect of the oral administration of disulfiram (DSF), a powerful antioxidant, on some blood test values of diabetes mellitus in OLETF rats. DSF (100 or 200 mg/kg body weight/day) was administered orally to rats once a day (5:00 PM) beginning when the rats were 7 weeks of age, and the plasma levels of glucose (PG), triglycerides (TG), total cholesterol (Total-cho) and insulin were measured from 10 to 38 weeks of age. The PG, TG, Total-cho and insulin levels did not change with aging in Long-Evans Tokushima Otsuka (LETO) rats, the strain used as a normal control. In contrast to the results in LETO rats, PG, TG and Total-cho levels all increased in OLETF rats with aging. The plasma insulin level in OLETF rats was also significantly higher than in LETO rats from 20 to 38 week of age. The Total-cho level in OLETF rats did not differ significantly between the saline and DSF administered groups. On the other hand, the oral administration of DSF attenuated the age-related increase in PG and TG levels in OLETF rats. In addition, the insulin level in DSF-administered OLETF rats was higher in comparison with saline-administered rats. The present study demonstrates that the oral administration of DSF to OLETF rats potently prevents the increase in PG levels and the decrease in insulin levels suggesting that DSF may provide effective therapy for type 2 diabetes mellitus.