Pancreatic Trypsin Output Research Articles

13C-egg white breath test: a non-invasive test of pancreatic trypsin activity in the small intestine

BACKGROUNDThe recent availability of egg white protein highly enriched with 13C has allowed breath test technology to be adapted for the study of protein digestion and absorption. Pancreatic trypsin is...

The effect of the cholecystokinin receptor antagonist MK-329 on meal-stimulated pancreaticobiliary output in humans

To determine the physiological role of circulating cholecystokinin (CCK), the effect of the CCK receptor antagonist MK-329 on upper digestive processes was investigated in six normal volunteers after a mixed meal. In a double-blind, two-period, randomized crossover design, the subjects received either 10 mg MK-329 or placebo orally 3 hours 15 minutes before the meal, which contained 51CrCl3 as food marker. A five-lumen tube with the tip in the distal duodenum allowed continuous marker infusion (57Co-B12) and duodenal aspiration as well as recordings of antral and duodenal motility patterns via three pressure sensors. Postprandially, MK-329 caused a significant reduction of 30%–60% (P < 0.05) in pancreatic trypsin output during the initial three 15-minute periods; thereafter, the output was virtually the same than after placebo. Thus, the integrated enzyme response was only reduced by 15% (NS) during the 3-hour period beginning 15 minutes after the meal. In contrast, gallbladder contraction, determined by total bile acid excretion, was inhibited by 77% (P < 0.05), indicating a crucial role of CCK in regulating gallbladder motility. Except for the initial 30 minutes postprandially, MK-329 also induced a significant reduction in duodenal pH with mean values ranging from 3.5 ± 0.2 to 4.1 ± 0.3 compared with 4.5 ± 0.3 to 5.0 ± 0.4 after placebo (P < 0.05), probably because of lowered secretion of pancreatic bicarbonate. Gastric emptying rate was significantly accelerated by MK-329 during the initial 75 minutes after the meal, but the time for 50% emptying did not differ from placebo [127.5 ± 7.7 vs. 140.0 ± 9.0 minutes (NS)]. No changes were observed in the motility pattern of the proximal duodenum after feeding. Whereas MK-329 only caused a slight increase of the basal plasma CCK concentrations, the postprandial levels were markedly enhanced. Peak concentrations were 10.0 ± 1.3 vs. 4.0 ± 0.5 pmol/L after placebo (P < 0.001), and the integrated response exceeded the control value by 175% (P < 0.01). The results suggest that circulating CCK is not an essential mediator of the postprandial pancreatic enzyme secretion in humans, whereas it plays a critical role in gallbladder emptying.

Atropine abolishes the potentiation effect of secretin and cholecystokinin-octapeptide on exocrine pancreatic secretion in humans.

Potentiating action between secretin and cholecystokinin on exocrine pancreatic secretion of bicarbonate has been well recognized. In the present study, we studied the effect of atropine on potentiating action on pancreatic exocrine secretion stimulated by exogenous secretin in physiologic dose and cholecystokinin-octapeptide in humans. Using a dye-dilution technique and a duodenal triple-lumen tube, pancreatic secretion of both bicarbonate and trypsin was determined while gastric juice was completely aspirated. Secretin given i.v. in a dose of 2.7 pmol/kg/h, which was known to achieve a similar plasma concentration of secretin after meal in humans, and cholecystokinin-octapeptide 26.2 pmol/kg/h potentiated pancreatic secretion of bicarbonate but not the pancreatic trypsin output. Atropine given i.v. in a dose of 1 mg/h abolished the potentiation effect of the two hormones on pancreatic bicarbonate output. Since the inhibitory effect of atropine on the secretin-stimulated bicarbonate output was statistically significant, the major inhibitory effect of atropine on the potentiation of pancreatic bicarbonate secretion appears to be its effect on the action of secretin.

Serum immunoreactive cationic trypsinogen: a useful indicator of severe exocrine dysfunction in the paediatric patient without cystic fibrosis.

We evaluated serum cationic trypsinogen as a marker of exocrine pancreatic function in children without cystic fibrosis. The ability of this test to determine steatorrhoea of pancreatic origin, and its relationship to a wide range of exocrine pancreatic function were assessed. Serum trypsinogen was measured in 32 children with steatorrhoea, 10 with pancreatic and 22 with non-pancreatic causes. In patients with pancreatic steatorrhoea, serum cationic trypsinogen was 4.9 +/- 4.9 micrograms/l (mean +/- SD), significantly below values in patients with non-pancreatic steatorrhoea (47.0 +/- 22.1 micrograms/l, p less than 0.001) and 50 control subjects (31.4 +/- 7.4 micrograms/l, p less than 0.001). Serum cationic trypsinogen values in patients with pancreatic steatorrhoea all fell below the lower limit of our control range and below all values for patients with non-pancreatic steatorrhoea. Serum cationic trypsinogen was also evaluated against pancreatic trypsin output in 47 patients (range 0.2-17.0 yr who underwent a hormonal pancreatic stimulation test. In 17 patients, serum cationic trypsinogen was low (less than -2SD or less than 16.6 micrograms/l), and associated with greatly impaired pancreatic trypsin output, ranging from 0-8% of mean normal trypsin output. Five of these 17 patients did not have steatorrhoea. In 30 patients with normal or raised serum cationic trypsinogen (greater than or equal to 16.6 micrograms/l), pancreatic trypsin output ranged from 15-183% of mean normal values. In conclusion, low serum cationic trypsinogen suggests severely impaired exocrine pancreatic function, with sensitivity extending above the steatorrhoeic threshold. In the presence of steatorrhoea, low serum cationic trypsinogen indicates a pancreatic aetiology. Normal serum cationic trypsinogen, however, does not exclude impaired pancreatic function, above the steatorrhoeic threshold.

Duodenal acidification releases cholecystokinin.

We studied the effect of hydrochloric acid (HCl) in the proximal small intestine on release of cholecystokinin (CCK) and secretin and on exocrine pancreatic secretion in conscious dogs with gastric cannulas and modified Herrera pancreatic cannulas. Intraduodenal administration of HCl in a concentration of 50 or 100 mM at rates of 0.05, 0.1, 0.2, and 0.4 mmol/min significantly increased plasma concentration of CCK in a dose-dependent manner, whereas plasma gastrin levels decreased. The increased plasma CCK level paralleled a significant increase in pancreatic trypsin output. Plasma secretin concentration and pancreatic bicarbonate output also increased in response to the acid, and the increase was dependent on the acid loads delivered in the duodenum. Thus, in dogs, HCl in the duodenum releases both CCK and secretin to stimulate pancreatic secretion of bicarbonate as well as enzymes.

Pancreatic enzyme response to a liquid meal and to hormonal stimulation. Correlation with plasma secretin and cholecystokinin levels.

Pancreatic trypsin output and plasma secretin and cholecystokinin (CCK) levels were measured in five healthy volunteers to investigate the mechanisms involved in regulating postprandial pancreatic secretion. The pancreas was stimulated by a liquid test meal or by either intravenous secretin (1-82 pmol/kg-1 per h-1) or caerulein, a CCK analogue (2.3-37 pmol/kg-1 per h-1), or by a combination of secretin and caerulein. Pancreatic secretion was assessed by a marker perfusion technique (polyethylene glycol [PEG 4000]), plasma secretin, and CCK by specific radioimmunoassays. Increasing doses of secretin produced increasing bicarbonate output (P less than 0.01), whereas trypsin was not stimulated over basal. Graded caerulein produced a stepwise increase in trypsin and bicarbonate output (P less than 0.01). Potentiation occurred for bicarbonate secretion between secretin and caerulein, but not for trypsin output. Postprandial trypsin secretion averaged 29.1 IU/min-1 over 150 min (equal to 55% of maximal response to caerulein). The peak trypsin response amounted to 90% of maximal caerulein. Significant increases of plasma secretion (P less than 0.05) and CCK (P less than 0.01) were observed after the meal. Comparison of enzyme and CCK responses to the testmeal or to exogenous caerulein suggested that the amount of CCK released after the meal could account for the postprandial trypsin secretion. We conclude that (a) the postprandial enzyme response in man is submaximal in comparison to maximal exogenous hormone stimulation; (b) CCK is a major stimulatory mechanism of postprandial trypsin secretion, whereas secretin is not involved; and (c) Potentiation of enzyme secretion is not a regulatory mechanism of the postprandial secretory response.

Perturbation of upper gastrointestinal function by cold stress.

To study the effects of stressful stimulus (cold pain) upon postprandial gastric, duodenal, and pancreatic function, nine healthy adult volunteers were intubated and then given two identical liquid meals, (199 cal (789 KJ) 240 ml), each being ingested during a period of irregular fasting gastroduodenal motility. Ten minutes after each meal the subjects received, in randomised order, either a test or control stimulus. The test stimulus consisted of repeated one minute immersions of a hand into ice water, with 15 seconds recovery between immersions, for a total of 20 minutes, while for the control, water at 37 degrees C was used. Serial samples of gastric and duodenal contents allowed estimation of changes in gastric emptying and acid secretion, together with pancreatic trypsin output, by a double marker perfusion technique. Measurements of blood pressure, pulse, and finger temperature acted as extra-intestinal indices of autonomic response to the stimuli. Cold pain significantly delayed gastric emptying and produced a biphasic alteration in both gastric secretion and pancreatic trypsin output, with an initial reduction during the response to the stress followed by an increase during the post-stress period. Our findings show that the normal postprandial function of the upper gut can be measurably disturbed by a stressful stimulus. The coincidence of these disturbances with other extra-intestinal autonomic changes suggests that they are a further manifestation of the somatic response to a stress.

Bile acid and pancreatic trypsin outputs are parallel during intraduodenal infusion of essential amino acids

There is disagreement as to whether contraction of the gallbladder occurs simultaneously with secretion of pancreatic enzymes during food ingestion. One study that employed exogenous cholecystokinin (CCK) alone showed dissociation of total bile acids (TBA) and trypsin outputs, while another study that employed exogenous CCK plus secretin showed parallel outputs of TBA and trypsin. Since previous studies have suggested that intraduodenal infusion of essential amino acids (EAA) evokes pancreaticobiliary secretion similar to that observed with food ingestion, we infused increasing doses of EAA intraduodenally in 10 subjects with intact gallbladder and in 10 subjects with previous cholecystectomy and measured total bile acids and trypsin outputs serially. In subjects with intact gallbladder, increasing molar doses of EAA induced parallel increases of TBA and trypsin outputs. In subjects with previous cholecystectomy trypsin outputs during infusion of EAA were similar to subjects with intact gallbladder, but their TBA outputs remained constant during the entire infusion period. Serial concentrations of plasma secretin did not change during intraduodenal infusion of EAA. These observations suggest that the gallbladder empties bile in concert with secretion of pancreatic enzymes following food ingestion.

Perturbation of Gastric Emptying and Duodenal Motility Through the Central Nervous System

This study was undertaken to test the hypothesis that external stimuli acting through the central nervous system perturb the normal gastrointestinal response to meals. Thus, in 4 healthy volunteers we used a multilumen gastroduodenal tube system that allowed simultaneous measurements of gastroduodenal motility, gastric emptying rate, gastric acid secretion, and pancreatic trypsin output. Blood pressure, pulse rate, and skin temperature were also monitored for autonomic response. All subjects were studied on 2 days, receiving on each day two identical test meals. After one of the meals on each day, vertigo was induced by labyrinthine stimulation (ear irrigation with ice water) while the other meal was followed by one of two controls, ear irrigation at 37 degrees C (control stimulation) on 1 day and no stimulation on the other, the order of the tests being randomized. Labyrinthine stimulation at subnauseant levels resulted in a consistent and reproducible delay in gastric emptying of the meal. Further, in 2 of the 4 subjects a marked and reproducible alteration of the postprandial duodenal motility pattern occurred, with a change to one resembling the fasted state, even though nutrients continued to be present in the stomach. Duodenogastric reflux and gastric acid output remained unchanged. Trypsin output decreased initially but later returned to control values. These studies emphasize the role of the central nervous system in the control of gut function after feeding. Labyrinthine stimulation nay be a useful method for investigating inhibitory and disruptive effects of centrally acting stimuli on the human upper gut.

Serum trypsin concentration and pancreatic trypsin secretion in insulin-dependent diabetes mellitus

Fasting serum trypsin concentration and pancreatic trypsin output, stimulated by secretin and cholecystokinin-pancreozymin, were measured in 18 patients with insulin-dependent diabetes, to assess a possible correlation between these two indices of exocrine pancreatic function. Serum trypsin concentration was subnormal in 13, and pancreatic trypsin output was decreased in 14 patients, but there was no significant correlation between the two measurements. There was no correlation between serum trypsin and residual beta cell function measured by plasma C-peptide immunoreactivity (CPR). After an interval of four years serum trypsin measurements were repeated in 11 subjects. All individual trypsin levels were lower than the previous results, the difference being highly significant ( t = 9.0; p < 0.001). Serum trypsin concentration therefore represents a qualitative index of reduced exocrine pancreatic function in diabetes, but has no value in quantitating the degree of deficiency.