Our aim was to isolate and determine the contribution of partial pancreatectomy, systemic delivery of pancreatic hormones, and duct obliteration to glucose regulation after segmental pancreas transplantation in dogs. Fasting, postprandial, and intravenous glucose-stimulated glucose, insulin, glucagon, pancreatic polypeptide (PP), and cholecystokinin (CCK) and intravenous bombesin-stimulated PP levels were studied in beagles at three successive intervals in a crossover design. The first was 6 wk after partial (∼70%) pancreatectomy with intact regular enteric exocrine drainage from the duodenal pancreatic remnant, the next was 2 wk after venous transposition with systemic delivery of pancreatic hormones, and the third was 6 wk after in situ duct obliteration of the remnant. With partial pancreatectomy, K values were modestly diminished (30%), and a concomitant reduction of second-phase intravenous glucose-stimulated insulin release was observed. Other parameters were not significantly affected. Venous transposition doubled peripheral plasma levels of insulin under all conditions. Fasting glucose, PP, and CCK levels decreased slightly. Other parameters were not affected. Duct obliteration of the systemic draining pancreatic remnants seriously impaired glucose sensitivity, resulting in a 50% reduction of K values and fasting and sustained postprandial hyperglycemia (∼8 mM) and a 70–50% reduction (acute and overall responses, respectively) of intravenous glucose-stimulated insulin. Fasting hormone and postprandial insulin, glucagon, and CCK levels were not affected. The postprandial PP response was severely reduced, and bombesin-stimulated PP release was abolished by duct obliteration. We conclude that histological changes associated with duct obliteration are the major determinants of glucose regulation in segmental pancreas transplantation. The defective acute insulin response to intravenous glucose is probably secondary to obliteration-induced intrinsic denervation of the islets, as supported by an abolished PP response to bombesin. The difference in the effect of duct obliteration on the insulin response to intravenous glucose and a meal may be related to the postprandial activation of the enteropancreatic axis.

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