Pancreatic Polypeptide and Intestinal Migrating Motor Complex in Humans

Abstract

There is a good correlation between pancreatic polypeptide release and pancreatic exocrine secretion in response to hormone and nutrient stimulation. During interdigestive periods, cyclic fluctuations of pancreatic and biliary secretions are associated with maximal activity (phase 3) of the intestinal migrating motor complex. In this study we determined whether the changes in fasting plasma pancreatic polypeptide levels are associated with secretory and motor events in the duodenum and the role of pancreatico-biliary secretion in pancreatic polypeptide release. Gastroduodenal motor activity, pancreatic enzyme and bile acid output, and plasma pancreatic polypeptide were studied in 10 fasting healthy subjects using the gastroduodenal intubation and perfusion method with strain-gauge pressure transducers positioned in the antrum, midduodenum, and jejunum. Four phases of duodenal interdigestive motor activity were identified. 'During phase 1 outputs of trypsin (5 ± 1 kU/h) and bile acid (72 ± 14 μ,mol/h) were minimal. During late phase 2, maximal output of trypsin (36 ± 4 kU/h) and bile acid (948 ± 268 μ,mol/h) occurred and continued into phase 3, followed by a rapid decline of trypsin (8 ± 2 kU/h) and bile acid (50 ± 12 μmol/h) secretion during phase 4. There were wide intra- and interindividual variations in fasting plasma pancreatic polypeptide concentrations. However these fluctuations appeared to be associated with cyclic changes of pancreatic and biliary secretions. Low plasma pancreatic polypeptide levels (26 ± 4 pg/ml) were present during phase 1, and levels started to increase during phase 2 (108 ± 10 pg/ml), reaching a peak in early phase 3 (143 ± 16 pg/ml). A rapid decline to low values (38 ± 6 pg/ml) occurred during phase 4. In a separate set of experiments in six healthy subjects, intraduodenal perfusion of pancreatico-biliary juice at 10 ml/min for 5 min, 30 min after a previous period of phase 3 motor activity, stimulated the release of pancreatic polypeptide (mean peak increase=166 ± 22 pg/ml) into the circulation. This was accompanied by an increased pancreatic trypsin and bile acid output similar to that observed during phase 3 activity. Neither the pH, osmolarity, nor protein content of the juice accounted for the response. We conclude that there are cyclic fluctuations of fasting plasma pancreatic polypeptide levels in humans that are associated with bursts of pancreatic and biliary secretion into the duodenum and maximal activity of the migrating motor complex in the proximal gut. There is an undefined factor(s) in the pancreatico-biliary juice that stimulates plasma pancreatic polypeptide release. These observations support the possibility that pancreatico-biliary secretion, pancreatic polypeptide release, and motor activity during the interdigestive period are causally related.