The Intestinal Phase of Pancreatic Polypeptide Release

Abstract

The purpose of this study was to determine whether nutrients in the small intestine cause a change in plasma pancreatic polypeptide concentration and, if so, the relative potencies of the major nutrient stimuli at different levels of the small intestine. We first compared the pancreatic polypeptide response to gastric and duodenal instillation of a test meal with that to ingestion of the same meal and modified sham feeding, in 10 healthy subjects. Intragastric feeding accounted for 70%, intraduodenal feeding accounted for 60%, and modified sham feeding accounted for 16% of the integrated pancreatic polypeptide response to meal ingestion. In separate experiments using a double-balloon intestinal perfusion technique, we examined the effects on plasma pancreatic polypeptide concentrations of 60-min infusions of isocaloric and isosmolar solutions of essential amino acids, oleic acid, and glucose in the upper, middle, and distal small intestine in random order in 7 healthy subjects. In the proximal small intestine, all three nutrients produced a significant rise in plasma pancreatic polypeptide concentrations, with a sequence of potency of: amino acids mixture (response = 3.04 ± 0.64 ng·min/ml), oleic acid (response = 1.25 ± 0.29 ng·min/ml), and glucose (response = 0.52 ± 0.14 ng·min/ml). The three nutrients retained their relative potencies in the middle small intestine, but were less effective than in the proximal segment (responses = 1.20 ± 0.26, 0.64 ± 0.12 and 0.39 ± 0.10 ng·min/ml for amino acids, oleic acid, and glucose, respectively). None of the nutrients perfused into the distal small intestine elicited a pancreatic polypeptide response. Thus, this study shows that the small intestine plays an important role in pancreatic polypeptide secretion which is dependent upon the nature of the nutrient and diminishes in effectiveness with distal progression. The demonstration of the existence of an enteropancreatic mechanism for the release of pancreatic polypeptide supports a possible physiologic role of pancreatic polypeptide as an inhibitor of postprandial pancreatic and biliary secretion.