Adaptation of the human pancreas to inhibition of luminal proteolytic activity.
OBJECTIVE
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 inhibitors 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.


METHODS
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, cholecystokinin plasma measurement, and standardized ultrasonographic investigations of the pancreas.


RESULTS
Duodenal trypsin output after secretion stimulation was significantly increased (+44%; P < 0.01) and duodenal bicarbonate 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 increased 62% (P < 0.05).


CONCLUSIONS
The human pancreas adapts to oral application of the proteinase inhibitor Camostate. These findings support the theory that feedback control of the exocrine pancreas operates in humans.
Friess
H
H
Department of Visceral and Transplantation Surgery, University of Bern, Bern, Switzerland.
Kleeff
J
J
Isenmann
R
R
Malfertheiner
P
P
Büchler
M W
MW
D000222:Adaptation, Physiological / Q000502:physiology*; D000328:Adult; D000681:Amylases / Q000097:blood; D001639:Bicarbonates / Q000378:metabolism; D002108:Ceruletide; D002766:Cholecystokinin / Q000097:blood; D004386:Duodenum / Q000201:enzymology; D004952:Esters; D005260:Female; D005502:Food; D016670:Gabexate / Q000031:analogs & derivatives*; D006146:Guanidines / Q000494:pharmacology*; D006801:Humans; D007515:Islets of Langerhans / Q000378:metabolism; D008049:Lipase / Q000097:blood; D008297:Male; D010179:Pancreas / Q000000981:diagnostic imaging / Q000187:drug effects / Q000201:enzymology* / Q000502:physiology*; D011480:Protease Inhibitors / Q000494:pharmacology*; D012633:Secretin; D014357:Trypsin / Q000378:metabolism; D014463:Ultrasonography
D001639:Bicarbonates; D004952:Esters; D006146:Guanidines; D011480:Protease Inhibitors; C034532:camostat; D012633:Secretin; D016670:Gabexate; D002108:Ceruletide; D002766:Cholecystokinin; D008049:Lipase; D000681:Amylases; D014357:Trypsin