EFFECT OF FK506 ON THE DEVELOPMENT OF DIABETES IN BB RATS IN COMPARISON WITH THAT OF CYCLOSPORINE

FK506, a agent extracted from a streptomyces, has more potent immunosu ppressive properties compared with cyclosporin in vitro. We compared t he preventive effect of FK506 on the development of diabetes mellitus with that of cyclosporin in BB rats, which are regarded as a useful mo del of insulin-dependent diabetes mellitus. BB rats aged 30 days were treated intramuscularly with FK506 (0.1 mg/kg/day and 0.32 mg/kg/day) or with cyclosporin (10 mg/kg, alternate days) until 150 days of age. Diabetes developed in 2 (10.5%) of 19 rats, treated with the lower dos e of FK506 and none of 20 rats with the higher dose of FK506; on the o ther hand, 1 (5.3%) of 19 rats treated with cyclosporin developed diab etes. In contrast, 9 (36.0%) of 25 control rats became diabetic. The c umulative incidence of diabetes mellitus in the group treated with FK5 06 (0.32 mg/kg) showed a decrease similar to or more than that of the cyclosporin-treated group. Histological examination showed that FK506 and cyclosporin prevented the reduction in the average size of islets and in the area of beta cells. The analysis of lymphocyte subsets prov ed the decrease of W3/25: OX8 ratio in both FK506- and cyclosporin-tre ated groups. These data suggest that the administration of FK506 might be a more useful tool for preventing the development of insulin-depen dent diabetes mellitus.