Transplantation of isolated islets of langerhans in diabetic dogs. I. Results after allogeneic intraportal islet transplantation

Abstract

Twenty partially inbred German shepherd dogs were made diabetic by intravenous administration of streptozotocin (25 mg/kg) 1 and 3 days after partial pancreatectomy. Ten diabetic dogs received intraportal transplants of allogeneic islets of Langerhans isolated by collagenase digestion and Ficon gradient separation. After transplantation the mean fasting serum glucose level fell from 368 ± 74 to 108 ± 52 mg/dl. Normal glycemia was maintained for at least 3 weeks before rejection occurred. The mean survival time of the 10 recipients was 76 ± 30 days, while the 10 diabetic control dogs had a mean survival time of 30 ± 7 days. Intravenous glucose tolerance test curves were clearly better in recipient dogs than in the diabetic control dogs for at least 4 weeks after islet transplantation. Concentrations of immunoreactive insulin (IRI) in the portal vein in the superior vena cava were also significantly higher than in the diabetic control dogs 4 weeks after islet transplantation. The mean peak concentration of IRI in the superior vena cava of transplanted dogs after glucose administration was higher than that in the portal vein, indicating that the transplanted islets secreted insulin in response to glucose stimulation. Portal hypertension or disturbance of liver function did not occur after transplantation of isolated islets. These results show that the intrahepatic site is appropriate for transplantation of isolated islets in a large animal model of diabetes, and provide a basis for future application in man.