Meal-Induced Pancreatic Polypeptide Release in a Validated Pancreatic Denervation Model

Abstract

In previous studies, postprandial pancreatic polypeptide (PP) release was diminished when pancreatic denervation was combined with distal pancreatectomy in animals without chronic fistulae. In contrast, postprandial PP release was reported to be unchanged when the pancreas was denervated without performing a distal pancreatectomy. These findings were unexpected given that the distal pancreas is a PP-poor region. To clarify this issue, we performed extrinsic pancreatic denervation, distal pancreatectomy, and insertion of chronic pancreatic fistulae in nine mongrel dogs. Insulin (0.5 U/kg) and meal-stimulated PP release were measured pre- and postoperatively. In addition, insulin- and meal-induced exocrine secretion was measured postoperatively. Preoperatively, insulin-induced hypoglycemia stimulated significant PP release (80,553 +/- 18,540 pg/min/ml). This response was completely abolished postoperatively (-1,669 +/- 5,054 pg/min/ml). Exocrine secretion did not increase above basal levels after administration of insulin in postoperative animals. These findings suggest adequate pancreatic denervation. Ingestion of a meal evoked significant PP response preoperatively (97,909 +/- 18,394 pg/min/ml). Postoperatively, the response was significantly blunted (17,231 +/- 6,407 pg/min/ml). This finding is in contrast to a previous report using a similar experimental preparation without distal pancreatic resection. We speculate that although the distal pancreas is PP-poor, it may play a role in the regulation of PP release from the PP-rich pancreatic head.