THE METABOLIC IMPACT OF RAPAMYCIN (SIROLIMUS) IN CHRONIC CANINE ISLETGRAFT RECIPIENTS

The objective of this study was to analyze the impact. of rapamycin an d/or cyclosporine, on the metabolic efficiency of intrasplenic islet a utografts in dogs, An insulin modified frequently sampled intravenous glucose tolerance test was carried out before, on the last of 30 days treatment with drug and 30 days after cessation of drug therapy in dog s with stable function 1 to 7 years after total pancreatectomy and int rasplenic islet autografting, Analyses were performed for glucose clea rance, insulin release, insulin sensitivity, and other variables. Rapa mycin treatment was associated with increased glucose clearance, incre ased total and stimulated insulin release in response to glucose, and increased fasting plasma insulin level, as well as reduced insulin cle arance, Cyclosporine at 300 mu g/L had Little impact on the measured v ariables. Treatment with rapamycin and cyclosporine showed a similar ( although less-marked) pattern of changes to rapamycin alone. Rapamycin , with or without concomitant cyclosporine, was not associated with ad verse impact on islet function or glucose metabolism in this canine mo del of pancreatic islet transplantation.