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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.

In segmental-pancreas transplantation the body and tail of the pancreas are used. In an experimental study in dogs, the effects of sequentially conducted removal of the right pancreatic lobe (pancreatic head), duct obliteration, celiac denervation, and autotransplantation were studied according to a crossover design. Two groups of dogs were studied. In both groups the right lobe of the pancreas was removed at primary operation, and the duct of the transected left lobe (body and tail) was injected with fibrin sealant. The left lobe was completely freed from surrounding tissue (celiac denervation) in group 1 (n = 9), and the innervation of the left lobe was left intact in group 2 (n = 8). At 12 wk, two dogs in group 1 and four dogs in group 2 underwent successful autotransplantation of the left lobe. Pancreatic hormone secretion was stimulated by intravenous glucose injection and test-meal administration before primary operation and at 11 and 18 wk thereafter. The combination of removal of the right lobe and duct obliteration led to a decrease in glucose tolerance at both stimulation tests and a decrease in peripheral insulin release after intravenous glucose injection. At test-meal administration, no change in insulin and glucagon levels was demonstrated. If ceiiac denervation was added, similar results were obtained based on the understanding that the peripheral insulin release after the test meal was significantly elevated. Meal-stimulated pancreatic polypeptide response was abolished in both groups. Removal of the right lobe leads to parasympathic denervation of the left lobe, and celiac denervation mainly interferes with α-adrenergic innervation. Cholecystokinin was probably responsible for the absence of a decrease in insulin secretion at test-meal administration after primary operation. Secondary autotransplantation led to elevation of peripheral insulin release at both tests but had no demonstrable influence on glucose tolerance expressed in K values.