ADAPTATION OF THE HUMAN PANCREAS TO INHIBITION OF LUMINAL PROTEOLYTICACTIVITY

Background & Aims: Feedback regulation of pancreatic enzyme secretion is well established in animals, and their pancreases are able to adapt to intraduodenal inhibition of pancreatic enzymes by proteinase inhib itors such as Camostate (FOY-305; Schwarz GmbH, Monheim, Germany). In this study, we addressed whether similar adaptive changes occur in the human pancreas after 4 weeks of 2 g/day Camostate application. Method s: Before, at the end of, and 2 weeks after 4-week Camostate treatment (four times 500 mg daily), pancreatic changes were analyzed with the use of a secretin-cerulein test, a test-meal stimulation, cholecystoki nin plasma measurement, and standardized ultrasonographic investigatio ns of the pancreas. Results: Duodenal trypsin output after secretion s timulation was significantly increased (+44%; P < 0.01) and duodenal b icarbonate output decreased 22% (P < 0.05) after 4 weeks of Camostate application. The size of the pancreatic head (vertical) increased 8% ( P < 0.05) at week 4 and decreased to pretreatment values 2 weeks after treatment (week 6). The other three diameters measured (head oblique, body, and tail) showed a similar pattern. Stimulated cholecystokinin plasma levels 15 minutes after application of a standard test meal inc reased 62% (P < 0.05). Conclusions: The human pancreas adapts to oral application of the proteinase inhibitor Camostate. These findings supp ort the theory that feedback control of the exocrine pancreas operates in humans.