Long-term function of isotransplanted islets of Langerhans in the diabetic rat

Highly inbred male rats were made diabetic by subtotal pancreatectomy. After diabetes developed, the animals were transplanted with an average of 500 isolated islets, obtained from donors of the same sex and strain, into the portal vein. Groups of islet-transplanted diabetic rats were followed for periods of 3, 6, and 14 months, during which time the performance of the transplanted islets was investigated. Control animals were followed for similar period of time. The findings obtained from each experimental group were integrated so as to provide a continuous picture of the transplanted islet's behaviour from 2 weeks to 14 months post transplantation. To assess islet performance, normal, untreated diabetic, and transplanted animals were subjected to three stimulatory tests of insulin secretion: (1) oral glucose tolerance, (2) intravenous sulfonylurea, and (3) intraperitoneal L-arginine. Normal and transplanted rats were additionally subjected to one inhibitory test of insulin secretion, diazoxide (given orally). At the end of the study, control and experimental animals were killed, and morphological investigations were performed on liver and pancreas. Isotransplantation of islets in partially depancreatized diabetic rats resulted in the reversal of the condition. The transplanted islets were found to respond to physiologic and pharmacologic controls, although the characteristics of the responses were not identical with that of the normal intact islet. The results of this study have suggested that a functional development of the transplanted islets occurs.