Islet transplantation: travels up the learning curve

Great excitement was generated in 2000 by a report from the University of Alberta in Edmonton, Canada, that seven of seven type I diabetic patients transplanted with intrahepatic cadaveric islets were normal glycemic, 1-year post-transplantation without the use of exogenous insulin treatment. The follow-up information from the same researchers with a larger group of patients indicated that in a group of 12 alloislet recipients, five had impaired glucose tolerance and three had post-transplantation diabetes. Great attention is now being directed toward understanding why alloislet recipients who are initially successful may later develop partial failure. At the same time, the Immune Tolerance Network is sponsoring a multicenter trial using the Edmonton protocol to ascertain whether these results can be replicated by other transplant groups in the United States, Canada, and Europe. Detailed studies of islet beta-cell function have revealed intact insulin secretion in autoislet and alloislet transplant recipients. In contrast, glucagon responses to insulin-induced hypoglycemia are absent from islets transplanted intrahepatically; however, alpha cells within intrahepatic islets are capable of releasing glucagon in response to intravenous arginine. Although many technical refinements are underway to make this procedure even more efficacious, supply and demand issues are a major concern and must be dealt with before the procedure of islet transplantation can be considered generally available for patients with diabetes.