Reduction of postprandial release of pancreatic polypeptide after development of pancreatic fibrosis.

We have measured the plasma pancreatic polypeptide response to a meal before and after the development of pancreatic fibrosis in dogs. Peripheral blood samples were collected in five dogs before and after a standard meal for measurement of pancreatic polypeptide by a specific radioimmunoassay. The next day, all of the pancreatic ducts were ligated in each dog, and one month after pancreatic ductal ligation, the food study was repeated. The dogs were sacrificed on the following day, and the pancreas of each dog was studied morphologically. Before pancreatic ductal ligation, plasma pancreatic polypeptide concentrations showed a biphasic response to a meal; a primary, rapid increase lasted 30 to 45 minutes, and a secondary, prolonged increase lasted for more than 180 minutes. One month after pancreatic ductal ligation, plasma concentrations of pancreatic polypeptide, at each time period during the initial 60 minutes after food, were significantly less than the corresponding sample before pancreatic ductal ligation. The total amount of pancreatic polypeptide released after a meal during the initial 60 minutes was diminished significantly by pancreatic ductal ligation. Neither plasma concentrations of pancreatic polypeptide nor the total amount of pancreatic polypeptide release after a meal showed a significant change during the last 180 minutes after food. Results of histologic observations showed destruction and fibrotic replacement of the acini of the pancreas after ligation of the pancreatic ducts. The islets were well preserved. Since the cells of origin of pancreatic polypeptide are distributed in both the acini and islets of the pancreas in dogs, we suggest that the primary, rapid phase of pancreatic polypeptide after a meal may be derived chiefly from cells in the acini, whereas the secondary phase of response may be derived chiefly from cells in the islets.