EFFECTS OF FK506 AND CYCLOSPORINE ON DYNAMIC INSULIN-SECRETION FROM ISOLATED DOG PANCREATIC-ISLETS

Pancreatic islet transplantation may be the most ideal treatment for p atients with insulin-dependent diabetes mellitus. However, immunosuppr essive agents such as cyclosporine A(CsA) and FK506, used for these tr ansplanted patients have been reported to cause glucose intolerance. I n the present study, we have compared the effects of CsA and FK506 on glucose-stimulated insulin release from the isolated dog pancreatic is lets, which have been maintained in culture for 3 days after isolation . The isolated dog pancreatic islets, pretreated for 24 hr with either CsA or FK506 (1, 10, and 100 nM), were perifused with 16.7 mM glucose . Pretreatment with both drugs suppressed glucose-stimulated insulin s ecretion in a dose-dependent fashion. CsA (100 nM), which is a therape utically relevant concentration, significantly suppressed both the fir st and second phases of glucose-stimulated insulin release compared wi th 100 nM FK506. These findings suggest that, with a therepeutically r elevant concentration, FK506 may be less toxic than CsA against pancre atic islets in patients with organ or cell transplantation.