Effect of FK506 on the development of diabetes in BB rats in comparison with that of cyclosporin.
FK506, a agent extracted from a streptomyces, has more potent immunosuppressive properties compared with cyclosporin in vitro. We compared the preventive effect of FK506 on the development of diabetes mellitus with that of cyclosporin in BB rats, which are regarded as a useful model 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 dose of FK506 and none of 20 rats with the higher dose of FK506; on the other hand, 1 (5.3%) of 19 rats treated with cyclosporin developed diabetes. In contrast, 9 (36.0%) of 25 control rats became diabetic. The cumulative incidence of diabetes mellitus in the group treated with FK506 (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 proved the decrease of W3/25: OX8 ratio in both FK506- and cyclosporin-treated groups. These data suggest that the administration of FK506 might be a more useful tool for preventing the development of insulin-dependent diabetes mellitus.
Wakugami
T
T
Second Department of Internal Medicine, School of Medicine, Faculty of Medicine, University of the Ryukyus, Nishihara.
Islam
M R
MR
Higa
S
S
Murakami
K
K
Mimura
G
G
D000375:Aging / Q000473:pathology; D000818:Animals; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D005260:Female; D005455:Fluorescent Antibody Technique; D016131:Lymphocyte Subsets / Q000276:immunology; D008297:Male; D010179:Pancreas / Q000473:pathology; D051381:Rats; D011913:Rats, Inbred BB; D016559:Tacrolimus / Q000009:adverse effects / Q000627:therapeutic use*
D016572:Cyclosporine; D016559:Tacrolimus