Feedback regulation of stimulated pancreatic enzyme secretion during intraduodenal perfusion of trypsin in man

Abstract

The pancreatic enzyme secretion in several species is controlled by a negative feedback mechanism induced by the presence of active proteases in the duodenum. The existence of this mechanism in man is controversial. The purpose of the present study was to evaluate the effect of tryptic activity in the duodenum on phenylalanine-stimulated pancreatic enzyme secretion in healthy volunteers. A double-balloon, multi-lumen tube was used for the collection of duodenal juice containing pancreatic enzymes. The continuous infusion of phenylalanine (100 mM) into the duodenum evoked an almost constant secretion of trypsin, amylase and lipase for 160 min. The infusion of trypsin (150 mg h-1; 1.25 g l-1) caused a reduction of phenylalanine-stimulated amylase and lipase output by 25%. The subsequent infusion of aprotinin at a dose of 1.5 X 10(6) KIU for 30 min led to an almost complete inhibition of trypsin. Simultaneously, the amylase and lipase output returned to the values seen before trypsin perfusion. Infusion of a higher dose of trypsin (300 mg h-1; 2.5 g l-1) caused a more pronounced decrease in phenylalanine-stimulated amylase and lipase output by 45%. These data indicate that active trypsin in the duodenum is responsible for the inhibition of phenylalanine-stimulated pancreatic enzyme secretion in man in a dose-dependent fashion, thus confirming the existence of a feedback control of pancreatic secretion regulated by the amount of proteases in the gut.