Negative Feedback Regulation Of Pancreatic Secretion Research Articles

Roles of gut hormones in negative-feedback regulation of pancreatic exocrine secretion in humans

Background/Aims: Secretin has been shown to mediate feedback control of pancreatic secretion of fluid and bicarbonate in rats, guinea pigs, and dogs. However, little is known about secretin in the feedback regulation in humans. We investigated the roles of secretin, cholecystokinin, neurotensin, and pancreatic polypeptide on feedback regulation of pancreatic secretion in 10 human volunteers. Methods: A 5-lumen tube was positioned in the proximal jejunum of fasting subjects under fluoroscopy so that gastric juice via lumen 1 and duodenal contents via lumen 3 were collected separately in 15-minute samples while polyethylene glycol solution was infused into duodenum via lumen 2. An acidified (pH 2.0) 4.25% amino acid mixed with phenol red was infused into proximal jejunum via lumen 4, which was alternated with NaHC03 (control solution) or trypsin (test solution) via lumen 5 intermittently every 15 minutes during separate test periods. Results: Infusion of control solution significantly increased both bicarbonate (total change [Δ], 7799 ± 1400 μmol/h) and chymotrypsin (Δ 5500 ± 762 μmol/h) outputs and levels of all four plasma hormones. The test solution significantly inhibited both bicarbonate (Δ 2999 ± 700 gmmol/h; P < 0.01) and chymotrypsin output (Δ 1000 ± 120 U/h, P < 0.01), which coincided with a significant suppression of plasma concentration of secretin and cholecystokinin but not pancreatic peptide and neurotensin. Conclusions: A negative-feedback regulation of pancreatic secretion of bicarbonate and enzyme occurs in humans and is mediated via both secretin and cholecystokinin.

Roles of gut hormones in negative feedback regulation of pancreatic exocrine secretion in humans

Abstract Background/Aims: Secretin has been shown to mediate feedback control of pancreatic secretion of fluid and bicarbonate in rats, guinea pigs, and dogs. However, little is known about secretin in the feedback regulation in humans. We investigated the roles of secretin, cholecystokinin, neurotensin, and pancreatic polypeptide on feedback regulation of pancreatic secretion in 10 human volunteers. Methods: A 5-lumen tube was positioned in the proximal jejunum of fasting subjects under fluoroscopy so that gastric juice via lumen 1 and duodenal contents via lumen 3 were collected separately in 15-minute samples while polyethylene glycol solution was infused into duodenum via lumen 2. An acidified (pH 2.0) 4.25% amino acid mixed with phenol red was infused into proximal jejunum via lumen 4, which was alternated with NaHC0 3 (control solution) or trypsin (test solution) via lumen 5 intermittently every 15 minutes during separate test periods. Results: Infusion of control solution significantly increased both bicarbonate (total change [Δ], 7799 ± 1400 μmol/h) and chymotrypsin (Δ 5500 ± 762 μmol/h) outputs and levels of all four plasma hormones. The test solution significantly inhibited both bicarbonate (Δ 2999 ± 700 gmmol/h; P P Conclusions: A negative-feedback regulation of pancreatic secretion of bicarbonate and enzyme occurs in humans and is mediated via both secretin and cholecystokinin.

Effect of pancreatic proteases on plasma cholecystokinin, secretin, and pancreatic exocrine secretion in response to sodium oleate

The effect of pancreatic proteases or juice on the sodium oleate-stimulated pancreatic secretion and plasma concentrations of secretin and cholecystokinin in anesthetized rats was investigated. Each rat received sodium oleate in a dose of 0.12 mmol · h−1 via a duodenal tube. Sodium oleate infusion significantly increased pancreatic secretion (volume and protein output) compared with the saline given the control group. The increase in pancreatic secretion paralleled significant elevations of plasma concentrations of secretin and cholecystokinin. To determine a possible role of pancreatic proteases on the responses induced by sodium oleate, saline, chymotrypsin, and trypsin, a combination of chymotrypsin and trypsin or pancreatic juice was infused into the duodenum. The pancreatic secretioo was significantly reduced by pancreatic proteases or pancreatic juice, and the reduction paralleled the decreases in plasma concentrations of the two hormones. These agents suppressed both pancreatic secretion and plasma hormone levels in the following order of magnitude: (pancreatic juice or chymotrypsin + trypsin) > (trypsin) > (chymotrypsin). The reduction of pancreatic secretion by pancreatic proteases was reversed by intravenous administration of secretin and cholecystokinin in physiological doses. It is concluded that negative-feedback regulation of pancreatic secretion is operative in the intestinal phase in rats and that both secretin and cholecystokinin are involved in the regulation.