Islet cell function in long‐term surviving primates after segmental pancreatic allotransplantation

Abstract

Islet cell function was studied in pancreatectomized primates with functioning segmental pancreatic allografts more than 100 days after transplantation. Segmental allograft recipients were immunosuppressed with total lymphoid irradiation (TL1) and cyclosporine (CSA). After 100 days, islet function was assessed, at which stage immunosuppression was terminated. Glucose, insulin, glucagon, and C-peptide response was assessed during intravenous glucose tolerance test (IVGTT) and during arginine and tolbutamide stimulation. In eight normoglycaemic primates in which immunosuppressive treatment had been stopped and with mean graft survival of 145 days, islet stimulation was associated with moderate glucose intolerance, reduced K-values, hypoinsulinaemia, and low C-peptide values. Postmortem findings in all animals intentionally killed revealed severe graft atrophy in the absence of significant rejection. Severe graft atrophy in normoglycaemic primates, together with significantly impaired graft function after segmental pancreatic transplantation compared to normal animals, suggest that transplantation of the whole pancreas may be mandatory if normal or near-normal function is to be achieved.

Nonhuman Primate Models for Islet Transplantation in Type 1 Diabetes Research

“…Numerous studies report allograft tolerance resulting from TLI followed by donor marrow injection in rodents as well as in nonhuman primates (e.g., Bieber et al 1979;Carver et al 1991). Indeed, the effectiveness of TLI in conjunction with islet allografts was reported in the 1980s (Du Toit et al 1988;Nash et al 1981). However, the practical application of this procedure still is suspect, due to inconsistent results and the necessity for immunosuppressive agents even after radiation treatment.…”

Pancreatic neuroendocrine tumors in twelve baboons (Papio spp.)

“…are very similar to humans and share approximately 96% genetic similarity . Baboons have been used for experimental studies affecting the endocrine system, including studies directly affecting the endocrine pancreas . Previous studies have documented the occurrence of pancreatic endocrine tumors in macaques and chimpanzees , owl monkey , colobus monkey , and baboons , with an incidence as high as 4.6% of all baboon tumors in one study , but the pathologic features of pancreatic endocrine neoplasms in Papio spp.…”