ROLES OF GUT HORMONES IN NEGATIVE-FEEDBACK REGULATION OF PANCREATIC EXOCRINE SECRETION IN HUMANS

Background/Aims: Secretin has been shown to mediate feedback control o f pancreatic secretion of fluid and bicarbonate in rats, guinea pigs, and dogs. However, little is known about secretin in the feedback regu lation in humans. We investigated the roles of secretin, cholecystokin in, neurotensin, and pancreatic polypeptide on feedback regulation of pancreatic secretion in 10 human volunteers. Methods: A 5-lumen tube w as positioned in the proximal jejunum of fasting subjects under fluoro scopy so that gastric juice via lumen 1 and duodenal contents via lume n 3 were collected separately in 15-minute samples while polyethylene glycol solution was infused into duodenum via lumen 2. An acidified (p H 2.0) 4.25% amino acid mixed with phenol red was infused into proxima l jejunum via lumen 4, which was alternated with NaHCO3 (control solut ion) or trypsin (test solution) via lumen 5 intermittently every 15 mi nutes during separate test periods. Results: Infusion of control solut ion significantly increased both bicarbonate (total change [Delta], 77 99 +/- 1400 mu mol/h) and chymotrypsin (Delta 5500 +/- 762 mu mol/h) o utputs and levels of all four plasma hormones. The test solution signi ficantly inhibited both bicarbonate (Delta 2999 +/- 700 mu mol/h; P < 0.01) and chymotrypsin output (Delta 1000 +/- 120 U/h, P < 0.01), whic h coincided with a significant suppression of plasma concentration of secretin and cholecystokinin but not pancreatic peptide and neurotensi n. Conclusions: A negative-feedback regulation of pancreatic secretion of bicarbonate and enzyme occurs in humans and is mediated via both s ecretin and cholecystokinin.