The Solution to Hyperglucagonemia after Pancreas Transplantation in Inbred Rats

Abstract

Background: We studied the possible role of the diseased host pancreas and site of venous graft drainage in the development of hyperglucagonemia after pancreas transplantation, to identify the crucial steps of the technique capable of eliminating hyperglucagonemia and its possible diabetogenic effect. Methods: Therefore, we compared 4 groups of inbred rats: (1) heterotopic pancreas transplantation with either systemic (n = 9); or (2) portal (n = 5) venous drainage after prior induction of diabetes with streptozotocin; (3) orthotopic pancreaticoduodenal transplantation with portal venous drainage after prior pancreaticoduodenectomy (n = 7), and (4) sham-operation (Sham; n = 10). The postoperative period was 6 months. Results: Only heterotopic transplantation with systemic venous drainage and loss of glucagon’s first pass hepatic extraction, resulted in arterial hyperglucagonemia, whereas the arterial plasma insulin level was only slightly higher in comparison with the other groups. After either type of heterotopic transplantation the glucagon content of host pancreata remained unchanged, whereas the insulin content was approximately 5% of that in the pancreas of Sham rats. The insulin and glucagon contents of all grafts were similar to those of the control pancreas in Sham rats, and the insulin release was sufficient to normalize fasting plasma glucose and lipids after either type of transplantation. Conclusion: To remove the diseased host pancreas appears unnecessary, as the hyperglucagonemia and the concomitant slight hyperinsulinemia, capable of preventing glucagon’s diabetogenic effects, are due to loss of the first pass hepatic extraction by systemic venous drainage alone. This disadvantage can be eliminated by portal venous graft drainage.