DIABETOGENIC EFFECTS OF FK506 ON RENAL SUBCAPSULAR ISLET ISOGRAFTS INRAT

Previously we demonstrated prevention of immune rejection in rat islet allografts by continuous subcutaneous (s.c.) administration of FK506 and also showed that FK506 might have diabetogenic effects (Ryu and Ya sunami (1991) Transplantation, 52, 599-605). The purpose of the presen t study was to characterize further diabetogenic effects of FK506 on r enal subcapsular islet isografts in rat. Continuous s.c. administratio n of FK506 (3 mg/kg/day) for 35 days produced glucose intolerance in t he recipients as demonstrated by intravenous (i.v.) glucose tolerance test at the end (35 days) and after discontinuation (90 days) of FK506 administration. Morphologically, beta cells in the grafts of FK506-tr eated group were degranulated at 35 and 120 days after transplantation . Electron microscopically, degranulation, marked swelling of rough en doplasmic reticulum, Golgi apparatus and mitochondria were detected in beta cells of the grafts treated with FK506 at 35 days, and at 120 da ys there was moderate structural recovery in the organella. These find ings clearly demonstrate that FK506 has diabetogenic effects on renal subcapsular islet isografts in rat and also suggests potential reversi bility of damages by FK506 in beta cells of the grafts.