Pancreatic proteases in the duodenum may exert feedback control of pancreatic exocrine secretion. It is not known if such a system is operative in man. In preliminary studies intraduodenal perfusion of trypsin inhibited phenylalanine-stimulated pancreatic enzyme secretion. We therefore propose to investigate the hypothesis that feedback regulation of pancreatic enzyme secretion by intestinal trypsin occurs in man. Using a gastrointestinal intubation perfusion method we plan to determine the effects of intraduodenal perfusion of trypsin and trypsin inhibitor on basal and phenylalanine-stimulated pancreatic enzyme secretion. The specificity of trypsin as an inhibitor of enzyme secretion will also be examined. In part II of the study we will investigate the hormonal and neural mechanisms responsible for feedback regulation. Cholecystokinin (CCK) is the hormonal stimulus and Pancreatic Polypeptide (PP) the inhibitor of enzyme secretion. Duodenal perfusion of pancreatic enzymes was associated with a fall in plasma CCK and rise in PP levels. Plasma CCK and PP responses to intraduodenal perfusion of phenylalanine with and without the addition of bovine trypsin will be determined. The effects of atropine and naloxone administration on the inhibitory action of tryspin in the duodenum will be examined. The validity of our hypothesis will be further tested in patients with pancreatic insufficiency in whom loss of feedback inhibition can be expected. If our hypothesis is correct we would expect raised CCK and low PP concentrations in the plasma of these patients and acute administration of trypsin in the duodenum should inhibit CCK and stimulate PP release. These studies should increase our comprehension of factors regulating pancreatic secretion and may provide insight into the pathogenesis of and therapeutic approach to chronic pancreatitis.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
2R01DK032838-04
Application #
3231183
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1983-08-01
Project End
1989-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
4
Fiscal Year
1986
Total Cost
Indirect Cost
Name
University of Michigan Ann Arbor
Department
Type
Schools of Medicine
DUNS #
791277940
City
Ann Arbor
State
MI
Country
United States
Zip Code
48109
Lu, Y; Owyang, C (2009) Secretin-induced gastric relaxation is mediated by vasoactive intestinal polypeptide and prostaglandin pathways. Neurogastroenterol Motil 21:754-e47
Owyang, Chung; Logsdon, Craig D (2004) New insights into neurohormonal regulation of pancreatic secretion. Gastroenterology 127:957-69
Li, Y; Jiang, Y C; Owyang, C (1998) Central CGRP inhibits pancreatic enzyme secretion by modulation of vagal parasympathetic outflow. Am J Physiol 275:G957-63
Takahashi, T; Owyang, C (1997) Characterization of vagal pathways mediating gastric accommodation reflex in rats. J Physiol 504 ( Pt 2):479-88
Li, Y; Owyang, C (1996) Peptone stimulates CCK-releasing peptide secretion by activating intestinal submucosal cholinergic neurons. J Clin Invest 97:1463-70
Owyang, C (1996) Physiological mechanisms of cholecystokinin action on pancreatic secretion. Am J Physiol 271:G1-7
Herzig, K H; Schon, I; Tatemoto, K et al. (1996) Diazepam binding inhibitor is a potent cholecystokinin-releasing peptide in the intestine. Proc Natl Acad Sci U S A 93:7927-32
Li, Y; Hao, Y; Owyang, C (1995) Evidence for autoregulation of cholecystokinin secretion during diversion of bile pancreatic juice in rats. Gastroenterology 109:231-8
Herzig, K H; Louie, D S; Owyang, C (1994) Somatostatin inhibits CCK release by inhibiting secretion and action of CCK-releasing peptide. Am J Physiol 266:G1156-61
Li, Y; Owyang, C (1994) Endogenous cholecystokinin stimulates pancreatic enzyme secretion via vagal afferent pathway in rats. Gastroenterology 107:525-31

Showing the most recent 10 out of 21 publications