Pancreatic Secretory Trypsin Research Articles

Physiological Evaluation of the Severity of Pancreatic Exocrine Dysfunction During Endoscopy

Despite the advances in pancreatic imaging, there continues to be a need to measure exocrine function to determine which patient requires enzyme supplementation. To evaluate the potential use of a rapid endoscopic test that can be conducted by nonacademic centers, we investigated whether concentration of trypsin in food-stimulated secretion is related to trypsin synthesis and secretion. Subjects include 22 chronic pancreatitis patients (10 mild, 5 moderate, and 7 severe radiological disease) and 11 healthy controls. During upper gastrointestinal endoscopy, pancreatic secretion was stimulated by a single 30-mL duodenal injection of an enteral diet, followed 5 minutes later by periampullary juice aspiration (endoscopic pancreatic function test [ePFT]). This was followed by a conventional 2-hour marker-perfusion diet-stimulated pancreatic trypsin secretion and synthesis study (2-hour PFT [2hPFT]). Severity of radiological disease was associated with a progressive loss of enzyme secretion measured by the 2hPFT. The endoscopic PFT correlated positively with 2hPFT (r2 = 0.48; P < 0.0001) and an activity of less than 5% of the average normal had a 96% specificity and 75% sensitivity for the detection of pancreatic insufficiency as defined by a loss of greater than 90% of pancreatic secretion. The diagnostic power of endoscopy may be enhanced by the collection of a pancreatic juice sample after enteral feed stimulation because measurement of the trypsin content will identify chronic pancreatitis patients who will be benefited by enzyme supplementation.

Enteral Feeding Without Pancreatic Stimulation

All forms of commonly practiced enteral feeding techniques stimulate pancreatic secretion, and only intravenous feeding avoids it. In this study, we explored the possibility of more distal enteral infusions of tube feeds to see whether activation of the ileal brake mechanism can result in enteral feeding without pancreatic stimulation, with particular reference to trypsin, because the avoidance of trypsin stimulation may optimize enteral feeding in acute pancreatitis. The pancreatic secretory responses to feeding were studied in 36 healthy volunteers by standard double-lumen duodenal perfusion/aspiration techniques over 6 hours. Subjects were assigned to no feeding (n = 7), duodenal feeding with a polymeric diet (n = 7) or low-fat elemental diet (n = 6), mid-distal jejunal feeding (n = 11), or intravenous feeding (n = 5). All diets provided 40 kcal/kg ideal body weight/d and 1.5 g protein/kg ideal body weight/d. Plasma gut peptide responses were monitored in 15 subjects. In comparison with basal fasting trypsin secretion rates (mean = 134 [standard error = 22] U/h), duodenal feeding with the polymeric and elemental formulae stimulated trypsin secretion (mean = 408 [standard error = 51] U/h; P < 0.001), whereas intravenous feeding (mean = 171 [standard error = 34] U/h) and mid-distal jejunal (mean = 119 [standard error = 16] U/h) did not. Stimulation was associated with an increase in plasma cholecystokinin, whereas distal jejunal feeding resulted in an increase in plasma glucagon-like peptide-1 and peptide YY concentrations. Our results suggest that enteral feeding can be given without stimulating pancreatic trypsin secretion provided it is delivered into the mid-distal jejunum. The mechanism may involve activation of the ileal brake mechanism.

Development of endocrine system regulating exocrine pancreas and estimation of feeding and digestive ability in Japanese eel larvae

To investigate the feeding and digestive physiology of early eel larvae, the development of cholecystokinin (CCK) and peptide YY (PYY) in the larval intestine, the feeding speed and pancreatic trypsin secretion in response to feeding were observed. CCK and PYY mRNA started to be expressed in the larval intestine at 8 days post-hatching (dph). This indicates that the pancreatic enzyme secretion is probably controlled by the CCK and PYY endocrine systems from the first feeding. Using fluorescein isothyiocyanate isomer (FITC)-labeled freeze-dried shark egg powder (Aquaran) as a diet, 10-dph eel larvae were estimated to feed at a rate of 0.04 μg Aquaran/min. The tryptic activity in the intestines of 11-dph larvae increased approximately 4.2-fold at 1 h of feeding, whereas that in the pancreas remained constant. These results indicate that the digestive tract of these larvae recognized Aquaran as a nutrient, and that the exocrine pancreas secreted digestive enzymes into the intestine and began to synthesize digestive enzymes in response to feeding.

Cholecystokinin and tryptic activity in the gut and body of developing Atlantic halibut larvae: evidence for participation in the regulation of protein digestion

At 7 days after first feeding (DAFF), the peptide hormone cholecystokinin (CCK) content (fmol individual−1) and the tryptic activity [μmol arginine‐methyl‐coumarinyl‐7‐amide (MCA) min−1 individual−1] per individual gut of Atlantic halibut Hippoglossus hippoglossus larvae were low: 0·2 ± 0·1 and 0·14 ± 0·10, respectively. Thereafter, both parameters increased with the increase in gut mass and reached 19·67 ± 5·58 and 2·71 ± 0·64 at 26 DAFF, respectively. Due to the small sample size, the dry mass (MG, mg) of the individual gut could not be determined accurately at 7 DAFF. At 13 DAFF MG represented 5·5% of whole body dry mass (Mw, mg) while at 26 DAFF it had increased to 23%. The mass specific tryptic activity [μmol MCA min−1 per mg dry mass (M)] in the gut increased from 2·74 ± 1 ± 98 at 13 DAFF to 5·00 ± 0·78 at 26 DAFF. There was more individual variation in the mass specific CCK content (fmol M−1) but no significant differences were found, although the data indicated an increase (from 23·38 ± 11·26 at 13 DAFF to 36·27 ± 8·96 fmol M−1 at 26 DAFF). At 7 DAFF the CCK content of the gut represented c. 2% of the whole body CCK content while it increased to c. 62% of the whole body CCK content at 26 DAFF. This demonstrates that it is necessary to separate neural and gastrointestinal sources of CCK in order to determine its alimentary role in fish larvae. Trypsin activity was only found in the gut compartment. In larvae aged 45 DAFF dietary proteins delivery into the gut by tube‐feeding appeared to stimulate post‐prandial secretion of CCK from the gut as well as stimulate pancreatic trypsin secretion, suggesting that both factors contribute to protein digestion.

High Dietary Lipid Levels Enhance Digestive Tract Maturation and Improve Dicentrarchus labrax Larval Development

This study was designed to determine the nutritional lipid requirement of seabass larvae and to understand the effects of dietary fat concentration on their digestive tract maturation. Seabass (Dicentrarchus labrax) larvae were fed, from d 15 to 38 of life, one of five isonitrogenous compound diets with different lipid levels, ranging from 10 to 30 g/100 g. The higher the lipid level, the greater the growth and survival of the larvae (P < 0.05). The lipolytic enzymes assayed, lipase and phospholipase A2, were stimulated by the increase in their respective dietary substrates, triglycerides and phospholipids, in 38-d-old larvae (P < 0.05). Nevertheless, a plateau in the activity of these two lipolytic enzymes was observed from 20% dietary lipids onwards. The similar mRNA levels of phospholipase A2 in the three groups fed the highest lipid levels suggested that the maximal synthesis level of lipolytic enzyme was reached at 20% dietary fat. Pancreatic secretion of trypsin and amylase were positively affected by the dietary lipid level; a possible involvement of a cholecystokinin-releasing factor is discussed. Diets containing >20% lipids led to the increase in activities of brush border membrane enzymes to the detriment of a cytosolic enzyme in enterocytes, leucine-alanine (Leu-Ala) peptidase. This enzymatic change reveals the earlier maturation of enterocytes in larva groups fed high lipid levels.

Comparison of the Kinetics of Pancreatic Secretion and Gut Regulatory Peptides in the Plasma of Preruminant Calves Fed Milk or Soybean Protein

Exocrine secretion from the pancreas and concentrations of cholecystokinin, gastrin, secretin, and somatostatin in plasma were measured in relation to feeding in 70- to 120-d-old preruminant calves fed either a milk diet or a soybean diet. Pancreatic fluid was continuously collected, measured, and reintroduced in catheterized calves. Blood samples were withdrawn for measurements of gut regulatory peptide concentrations in plasma. A slight increase in outflow of pancreatic fluid was observed 30min before the milk diet was introduced but not before the soybean diet was fed. In contrast, concentrations and outflows of protein and trypsin immediately after feeding were higher when calves were fed the soybean diet. Overall, during the first 5h postfeeding, the outflow of pancreatic fluid was 40% higher when the milk diet was fed than when the soybean diet was fed. No difference in outflow of protein was observed, but that of trypsin was 82% higher when the soybean diet was fed. This enhanced enzyme secretion could have been related to the increased plasma concentrations of gastrin and cholecystokinin after the soybean diet was fed. Secretin release was less in calves fed the milk diet that in calves fed the soybean diet during the first 2h postfeeding, suggesting that this gut peptide along with gastrin and cholecystokinin, contributed to the stimulation of enzyme secretion. Plasma gut regulatory peptides could be influenced by the soybean diet, which does not coagulate in the stomach, inducing faster gastric emptying of protein and fat, and by the chemical form of protein from the soybean diet and the lower susceptibility of these proteins to protease compared with casein. However, the resulting enhancement of pancreatic trypsin secretion and activity seemed to be insufficient to increase the digestibility of soybean protein up to a level similar to that of milk.

Adrenergic modulation of interdigestive pancreatic secretion in humans

Whether the adrenergic pathways participate in the control of interdigestive pancreatic function in humans is uncertain. To determine if changes in α-or β-adrenergic tone modulate interdigestive pancreatic enzyme output, 16 healthy subjects were intubated with an orojejunal tube to collect and quantify pancreatic trypsin secretion and record motility. After observation of a complete interdigestive cycle (control period), eight groups of two subjects each received 2-hour intravenous infusions of the α- and β-agonist epinephrine (50 ng · kg−1 · min−1), the α-antagonist phentolamine (5 mg/2 min followed by 500 μg/min), the β-antagonist propranolol (5 mg/2 min followed by 80 μg/min), or saline as control, alone or in combination. Drugs were assigned in a random mode according to a 23 factorial design. Analysis of variance showed that epinephrine decreased trypsin output by 43% (P < 0.05). By contrast, trypsin output was increased fourfold in the presence of phentolamine (P < 0.01), whereas propranolol had no effect. These data suggest that an inhibitory α-adrenergic tone modulates human interdigestive pancreatic enzyme secretion whereas β inputs are less important.

Stimulatory Effects of Bombesin on Plasma Trypsin Release and Exocrine Pancreatic Secretion in Dogs

We examined the effect of bombesin on plasma trypsin release and exocrine pancreatic secretion in dogs. Bombesin significantly increased plasma immunoreactive trypsin (IRT). Atropine significantly inhibited the response of plasma IRT to bombesin. Pancreatic trypsin secretion was also increased by bombesin, as well as bicarbonate and protein outputs. Atropine failed to inhibit pancreatic trypsin secretion. In conclusion, bombesin has a stimulatory effect on plasma trypsin release mediated by a cholinergic mechanism and different from pancreatic secretion.

Oxyntomodulin from distal gut

We studied the effects of intravenous infusion of synthetic oxyntomodulin (proglucagon 33-69), a potential hormone from the ileal mucosa, on fasting and postprandial gastric acid secretion, gastric emptying, gastroduodenal motility, and pancreatic secretion of trypsin and lipase measured simultaneously in six normal volunteers using multilumen tubes for infusion of markers, manometry, and aspiration of gastric and duodenal contents. The infusion resulted in plasma concentrations of 203 +/- 21 pmol/liter (mean +/- SEM) of oxyntomodulin, regarded as high but not unphysiological concentrations of the peptide. Oxyntomodulin almost abolished basal acid secretion and inhibited postprandial acid secretion by 35 +/- 10%. Gastric emptying decreased significantly; the time for 50% to leave the stomach increased from 17.3 +/- 2.2 min to 34.7 +/- 8.0 min. The postprandial gastroduodenal motility was massively inhibited by oxyntomodulin. Postprandial trypsin and lipase output was significantly inhibited by 56 +/- 12% and 42 +/- 11%, respectively, during oxyntomodulin infusion. However, pancreatic enzyme output was linearly related to gastric emptying and oxyntomodulin did not influence this relationship, suggesting that oxyntomodulins effect was due to its effect on gastric emptying. Oxyntomodulin seems to play an important role in the small intestinal inhibitory control of gastropancreatic functions.

Impaired pancreatico-biliary response to vagal stimulation and to cholecystokinin in human obesity

We previously found that massively obese patients respond with less gastric acid secretion in response to vagal stimulation. This is compatible with the described association between experimental obesity and altered vagal function in the rat. To confirm this observation, the pancreatic and biliary responses to vagal stimulation were examined in nine nondiabetic obese patients against a background secretin infusion of 15 CU × h −1, and monitored after a subsequent injection of 75 IDU of cholecystokinin. Two separate marker perfusion systems were used in the stomach and duodenum, respectively, and blood samples were drawn for hormone analyses. In contrast to controls having normal body weight, the obese patients failed to respond with increments of pancreatic enzyme secretion and duodenal bile acids after stimulation with modified sham feeding. Cholecystokinin stimulated the pancreatic secretion of trypsin, amylase, and lipase, the emptying of bile acids, and the release of gastrin, but the patients' responses were only half that of the controls. In the resting state the obese had higher outputs of bile and pancreatic enzymes and higher plasma levels of pancreatic polypeptide compared with controls, but the pancreatic bicarbonate secretion rate was not different. The almost complete suppression of the basal gastric acid secretion by a low dose of intravenous (IV) secretin in controls did not occur in the obese. We conclude that massive obesity is associated with a reduced pancreatic and biliary response to vagal stimulation. Compared with controls, the digestive functions of the obese patients seem to be less sensitive to stimulation by exogenous cholecystokinin. In addition, the normal release pattern of digestive hormones in the resting state and after stimulations showed multiple alterations in massive obesity.

The acute effects of coffee and caffeine on human interdigestive exocrine pancreatic secretion.

The effects of coffee on exocrine pancreatic secretion are unknown but may be important, because a link between chronic stimulation of pancreatic secretion and experimental chemical carcinogenesis and an association between coffee drinking and human pancreatic adenocarcinoma have been reported. We measured exocrine pancreatic trypsin and gastric acid secretions collected through orogastroduodenal tubes and serum gastrin in eight non-coffee drinkers and eight coffee drinkers. During fasting, after one interdigestive cycle control period, one of four 250-ml samples [plain water, water plus caffeine (4.6 mg/kg), decaffeinated coffee (127.9 mg/kg), caffeinated coffee (127.9 mg/kg)] was administered through the orogastric tube. Caffeinated and decaffeinated coffee (p = 0.008), caffeine (p = 0.03), and an unidentified substance(s) in coffee other than caffeine (p = 0.008) were associated with increased interdigestive exocrine pancreatic trypsin secretion. In addition, we also confirmed that coffee and caffeine stimulated gastric acid secretion (p = 0.02) and decaffeinated coffee raised serum gastrin concentrations (p = 0.005). If an association between coffee and pancreatic carcinogenesis exists, chronic stimulation of the exocrine pancreas by secretagogues could result in a gland susceptible to carcinogenesis.

Bile exclusion from the duodenum

The effect of diverting bile from the duodenum in four dogs with cholecystojejunostomy was studied using a double-marker perfusion technique. After the diversion procedure, a liquid meal increased acid secretion from 0.8 mmol H+/min to 1.48 mmol H+/min (P less than 0.05, paired t test); there was an associated rise in serum levels of gastrin 120 min after feeding (P less than 0.001, paired t test). Pancreatic secretion of trypsin decreased from 3.91 IU/min to 2.66 IU/min after bile diversion (P less than 0.01, paired t test), and the level of CCK was significantly lower 60 min after feeding (P less than 0.05, paired t test). There was no significant change in the rate of gastric emptying after bile diversion, but the pH of duodenal contents was lower in the later stages of digestion. These changes may explain the reported increase of peptic ulcer after diverting bile from the duodenum, and the procedure should not be considered unless the consequences of acid hypersecretion and pancreatic inhibition have been anticipated.

Increased interdigestive pancreatic trypsin secretion in alcoholic pancreatic disease

Previous studies have suggested that chronic alcohol consumption in man is associated with an increased secretion of pancreatic enzymes. Precise quantitation of the output of protein and trypsin in the interdigestive state has not been possible because of large variations and small volume of pancreatic juice. We utilized a multilumen, marker-perfused duodenal catheter to simultaneously monitor intraluminal pressures and collect mixed duodenal juice at the ligament of Treitz in five groups of patients: normal volunteers (group I), alcoholics without pancreatitis (group II), alcoholics who had recovered from acute pancreatitis (group III), alcoholics with chronic pancreatitis (group IV), and nonalcoholics who had recovered from acute pancreatitis secondary to biliary tract disease (group V). The output of trypsin and protein during 30 min of phase II and 60 min of CCK-OP 40 ng/kg/hr was determined in each group. The output of trypsin during phase II was 1.3 +/- 1.2 and 3.0 +/- 2.5 mg/kg/hr in groups II and III, respectively, compared to 0 +/- 0.1 in group IV (normal = 0.6 +/- 0.5). The outputs in group V were similar to normals. The output of protein during the interdigestive state was 15.7 +/- 13.7 mg/min in group III, compared to 4.5 +/- 3.6 in normals (group I). The duodenal contraction rate was 4.6 +/- 3.0 and 3.3 +/- 2.7 contractions/min in groups III and II, respectively (significantly greater than the normal rate of 2.2 +/- 1.5).(ABSTRACT TRUNCATED AT 250 WORDS)

Potentiation Effect of Cholecystokinin-Octapeptide on Pancreatic Bicarbonate Secretion Stimulated by a Physiologic Dose of Secretin in Humans

We studied the potentiation effect of cholecystokinin-octapeptide and secretin on pancreatic secretion of bicarbonate and trypsin in humans. The pancreatic bicarbonate and trypsin outputs were determined by using a triple-lumen duodenal tube and indicator dilution technique while gastric juice was completely aspirated. When cholecystokinin-octapeptide in varied doses, 2.6, 5.3, 10.9, 26.3, 52.6, and 109.4 pmol . kg-1 . h-1, was added to i.v. infusion of secretin in a physiologic dose, 0.03 clinical units (CU) . kg-1 . h-1, the bicarbonate outputs were significantly greater than those achieved by secretin or cholecystokinin-octapeptide alone or the sum of the bicarbonate outputs produced by each hormone. The potentiation effect of cholecystokinin-octapeptide occurred at the dose of 10.9 pmol . kg-1 . h-1. No further further augmentation on the bicarbonate output occurred when the dose of cholecystokinin-octapeptide was increased in the dose range greater than 10.9 pmol . mg-1 . h-1. No potentiation on pancreatic secretion of trypsin was apparent when the two hormones were given simultaneously. Thus, cholecystokinin-octapeptide in a relatively small dose range potentiated the pancreatic bicarbonate secretion stimulated by a physiologic dose of secretin. The pancreatic enzyme secretion does not appear to be potentiated by two hormones.

Correlation Between Pancreatic Enzyme Secretion and Plasma Concentration of Human Pancreatic Polypeptide in Health and in Chronic Pancreatitis

We have determined the relationship between pancreatic enzyme secretion and release of pancreatic polypeptide in response to nutrient and hormone stimulation in healthy subjects and in patients with different degrees of chronic pancreatitis. In 8 healthy subjects, the output of trypsin, in response to intraduodenal perfusion of an essential amino acid mixture (39.6 ± 3U/h) was significantly higher than that in response to oleic acid (30. 5 ± 1.6 U/h), which in turn was greater than the response to glucose (11.3 ± 2.3 U/h). The relative potencies of the three nutrients in the stimulation of pancreatic polypeptide secretion were similar to those observed for pancreatic enzyme secretion. The integrated pancreatic polypeptide responses were 3206 ± 317, 1954 ± 147, and 1236 ± 117 pg/min · ml for amino acids, oleic acid, and glucose, respectively. The mean (±SE) increase in trypsin output in response to cholecystokinin octapeptide stimulation (35.6 ± 6.4 U/h), was significantly greater than that observed in response to either secretin (9.4 ± 3.0 U/h), or pentagastrin stimulation (10.2 ± 5.9 U/h). The patterns of pancreatic polypeptide responses were similar to those observed for pancreatic trypsin secretion (integrated plasma pancreatic polypeptide response=3127 ± 722; 1261 ± 488; 1207 ± 383 pg/min · ml for cholecystokinin octapeptide, secretin, and pentagastrin, respectively). Over the range of pancreatic enzyme secretion there was a linear relationship between the mean increase in trypsin output in response to each nutrient and the corresponding integrated plasma pancreatic polypeptide response (r = 0.83, p

Interdigestive canine pancreatic juice composition and pancreatic reflux and pancreatic sphincter anatomy.

Canine and human exocrine pancreatic secretion into the duodenum during fasting is cyclical and related to intestinal motility. To characterize the composition of pure pancreatic juice during the cyclically recurring sequence of propagated motor events (interdigestive motor complex) and to establish whether pancreatic reflux occurs, dogs were prepared with three permanent indwelling duodenal catheters and a pancreatodochal cutaneous catheter. The duodenal catheters were used to record duodenal pressures and measure pancreatic secretion of trypsin, lipase, and bicarbonate, based on the recovery of a constantly perfused marker, [14C]PEG. Pancreatic duct pressures or pancreatic juice concentrations of [14C]PEG, trypsin, lipase, or bicarbonate (done separately in each of five dogs throughout one interdigestive cycle on 4 different days) were related to duodenal motor activity. Finally, the pancreatic duct orifice of freshly sacrificed dogs was examined by light and electron microscopy. During fasting, (1) pancreatic volume secretion increased 10-fold during phases II, III, and IV (P less than 0.001), and bicarbonate concentration increased during phases III and IV (P less than 0.05) compared with phase I, while trypsin and lipase concentrations did not change; (2) reflux of duodenally perfused [14C]PEG into the pancreatic duct occurred in two of five dogs and was minimal (less than 0.1%); and (3) a positive mean pressure gradient from duodenum to pancreatic duct occurred only during phase III (7.4 +/- 4.1 cm H2O). Anatomic studies of the pancreatic duct opening showed a specialized papillary mucosa and an independent crescentic sphincter muscle. We conclude that during fasting, pancreatic juice composition is intimately linked to the different phases of interdigestive intestinal motor activity and that an efficient antireflux mechanism exists.

The effect of hyperthyroidism on gastric emptying rates and pancreatic exocrine and biliary secretion in man.

Malabsorption and diarrhea in hyperthyroidism has been attributed in part to an increased rate of gastrointestinal transit as measured with barium sulfate suspension. Data are unavailable on the effect of hyperthyroidism on gastric emptying rates of normal food and pancreatic enzyme secretion. These functions have been studied in 4 hyperthyroid patients and compared to results obtained when treatment achieved euthyroidism. Pancreatic trypsin secretion was half the euthyroid level in the hyperthyroid state. No significant change in bile salts occurred, although there was a tendency for a greater proportion of dihydroxy bile salts while hyperthyroid. Gastric emptying rates of a mixed fat, protein, and carbohydrate liquid meal were normal. Similarly the gastric emptying rate of a beef stew plus chicken liver meal was normal. We conclude that in hyperthyroidism gastric emptying rates of "physiologically active" food is normal. Pancreatic enzyme secretion is depressed in hyperthyroidism and may contribute to maldigestion.