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This study was designed to assess plasma glucose levels (PLG) and insulin release in totally pancreatectomized baboons when challenged with intravenous glucose administration (IVGTT). Ten animals (Papio ursinus) were used and duodenectomy was intentionally avoided. The PLG at death was 18.0 +/- mmol/L, and the mean K-value within 3 days after pancreatectomy was 0.4% +/- 0.2%, indicating a significant impairment of glucose disappearance from the blood when compared to the control animals (P less than 0.01). Plasma insulin levels before and after stimulation with glucose were below the lowest level of insulin assay sensitivity. We conclude that in the primate, as in the dog, surgical pancreatectomy produced a reliable diabetic model, which is uniformly lethal if left untreated.

The object of this preliminary study was to evaluate the endocrine function after heterotopic intraperitoneal segmental pancreatic allotransplantation with unligated duct in irradiated, totally pancreatectomized primates. All allograft recipients received, pre- and peroperative donor-specific blood transfusions and peroperative external irradiation from a linear accelerator; 200 rads was administered weekly and increased to a total dose of 1,500 rads. Pancreatic transplantation was performed between 2 and 6 weeks after completion of irradiation and preoperative blood transfusions. As previously reported, only minimal pancreatic allograft survival was achieved following preoperative irradiation. One recipient remained normoglycaemic for greater than 100 days after transplantation, the longest surviving pancreatic allograft recipient reported from this laboratory. Intravenous glucose tolerance test results in this recipient revealed normoglycaemia, reduced K-value, hypoinsulinaemia, normal glucagon response, reduced C-peptide values, and moderate glucose intolerance. Aortography and electron-microscopic examination of allograft biopsy tissue confirmed the presence of a functioning allograft.

In this study we evaluated the endocrine, biochemical, and haematological derangements as well as pancreatic and histological changes of the bonemarrow in the primate following external fractionated subtotal marrow irradiation without bonemarrow reconstitution. The irradiation was administered in preparation for pancreatic transplantation. Two groups of animals (ten in each group) received 800 rad (8 Gy) and 1,000 rad (10 Gy) respectively over 4 to 5 weeks. A maximum of 200 rads (2 Gy) were administered weekly as photons from a 6 MV linear accelerator. During irradiation the animals remained normoglycaemic in the presence of transiently elevated liver enzymes and serum amylase values, which returned to normal on completion of the irradiation. Insulin release was significantly reduced in both groups during irradiation and was associated with minimally decreased K-values in the presence of mild glucose intolerance. Pancreatic light morphologic changes included structural changes of both exocrine and endocrine elements and included necrosis of the islet cells and acinar tissue. Islet histology demonstrated striking cytocavitary network changes of alpha and beta cells, including degranulation, vacuolization, mitochondrial destruction, and an increase in lysosomes. A hypoplastic bonemarrow ranging from moderate to severe was observed in all irradiated recipients. Near total fractionated body irradiation in the primate is therefore associated with elevated liver enzymes, pancytopenia, transient hyperamylasaemia, hypoinsulinaemia, a varying degree of pancreatitis, and bonemarrow hypoplasia.

In this study we evaluated the short-term hormonal effects of segmental and whole pancreatic allotransplantation on the glucose intolerance produced by hemipancreatectomy in the primate. In hemipancreatectomized animals without grafts the K-values were reduced to 0.6 +/- 0.05, plasma insulin increased from 27.5 +/- 2.5 to 63.5 +/- 6.3 microU/ml, and glucagon levels declined from 252 +/- 29.9 to 216.5 +/- 33.0 pg/ml. Hemipancreatectomized segmental allograft recipients rendered K-values of 0.79 +/- 0.05, plasma insulin increased from 19.98 +/- 3.43 to 66.0 +/- 17.03 microU/ml, and glucagon release declined from 395.6 +/- 63.0 to 226.2 +/- 37.6 pg/ml during IVGTT postoperatively. Hemipancreatectomized, pancreaticoduodenal allograft recipients rendered K-values of 0.82 +/- 0.1, results not significantly different from hemipancreatectomized or segmental allograft recipients. Plasma insulin increased from 29.5 +/- 4.0 to 186.0 +/- 25.0 microU/ml, and glucagon release declined from 1,087.0 +/- 31.6 to 656.0 +/- 12.7 pg/ml. In summary, segmental pancreatic allotransplantation could not, in the short-term, restore the reduced K-values and hypoinsulinaemia in hemipancreatectomized primates to that of normal, unstressed controls. Although K-values of hemipancreatectomized recipients were not significantly improved, whole pancreas transplantation resulted in improved insulin release and hyperglucagonaemia during IVGTT when compared to segmental allograft recipients. The unexpected findings of hypoinsulinaemia and hyperglucagonaemia in both transplant groups may only reflect a function of the stressed state of the animals in the immediate postoperative phase.