Volume Of Pancreatic Juice Research Articles

Effect of natural peptide YY on blood flow and exocrine secretion of pancreas in dogs.

Little is known regarding the mechanism by which peptide YY exerts an inhibitory effect on exocrine pancreatic secretion. The purpose of this study is to determine if peptide YY affects pancreatic blood flow with simultaneous measurement of exocrine pancreatic secretion in dogs. Pancreatic blood flow was measured by a laser Doppler flowmeter which allows continuous measurement of tissue blood flow. Natural peptide YY (0.1, 0.5, 1 microgram/kg) was infused intravenously as a bolus under background infusion of secretin (1 unit/kg/hr) in combination with cholecystokinin-octapeptide (0.1 microgram/kg/hr). Peptide YY caused a reduction of pancreatic blood flow in a dose-dependent manner as well as inhibition of pancreatic protein output, attaining the maximal reduction (28 +/- 4%) and inhibition (45 +/- 9%) at a dose of 1 microgram/kg, respectively. Simultaneous and continuous observation on tissue blood flow and exocrine secretion of the pancreas revealed that there was a highly significant correlation between the percent reduction of pancreatic blood flow and that of volume of pancreatic juice in response to peptide YY (r = 0.849, P less than 0.001). This study provides evidence that the mechanism of peptide YY-induced inhibition of exocrine pancreatic secretion is mediated, at least partly, through the decreased pancreatic blood flow.

Different effects of intraperitoneal or subcutaneous administration of H2-antagonists on pancreatic response to chronic administration of caerulein in rats.

This study deals with the effect of H2-receptor antagonists on pancreatic response to chronic administration of caerulein. Caerulein was administered alone or combined with cimetidine, ranitidine or famotidine twice a day in various regimes. At the end of treatment, pure pancreatic juice was collected after hormonal stimulation. Then, the rats were killed, and growth and composition of the pancreatic tissue were determined. Caerulein increased pancreatic weight and enzyme content as well as volume and enzyme activity of pancreatic juice. When given alone the three H2-receptor antagonists were totally ineffective. Both ranitidine and famotidine, but not cimetidine, significantly reduced pancreatic response to chronic administration of caerulein only when given intraperitoneally together with caerulein. On the contrary, separate applications of caerulein and ranitidine (or famotidine) did not influence caerulein-stimulated pancreatic growth or enzyme secretion. Moreover, in rats treated both intraperitoneally and subcutaneously with caerulein, the H2-antagonists reduced the pancreatic response only partially and in proportion to the intraperitoneal dose of caerulein. The responsiveness of pancreatic tissue to subcutaneous caerulein was not modified. The results suggest that H2-receptor antagonists induce (1) impaired uptake of caerulein when given together with peptide, but (2) have no specific inhibitory effect on pancreatic response to caerulein.

Morphological and biochemical changes in the pancreas of copper-deficient rats.

Two types of experimental chronic pancreatic damage were induced in rats by a copper-deficient diet containing D-penicillamine (DP rats) and by a similar diet without D-penicillamine (D rats). At 5-6 weeks after commencement of treatment, serum copper levels showed a significant decrease in both DP rats (1.5 +/- 0.9 micrograms/dl, M +/- SE) and D rats (18.8 +/- 1.4 micrograms/dl) compared with the findings in control rats (111.8 +/- 4.4 micrograms/dl). Histology revealed loss and atrophy of acinar cells in DP rats and mild vacuolar degeneration of acinar cells in D rats, whereas the islets of Langerhans were intact in both groups. The secretion of the exocrine pancreas showed a marked decrease in enzymes and protein output in DP and D rats compared with findings in the control rats. Our study confirmed the relationships between serum copper levels and morphological damage of pancreatic acinar cells or the reduction of enzyme secretion. On the other hand, the reductions in volume and bicarbonate output of pancreatic juice in DP rats and in D rats were detected, but no relationship was found between these reductions and the serum copper levels. The endocrine pancreatic function in DP rats showed a slight disturbance in intravenous glucose tolerance test. These results support the conclusion that copper-deficiency causes disturbances in enzyme-synthesis and selective destruction of acinar cells.

The Influence of Diets Based on Whole Wheat, Wheat Flour and Wheat Bran on Exocrine Pancreatic Secretion in Pigs

Six pigs, initially 40 kg live weight, were prepared with a duodenal pouch for collection of pancreatic juice to assess the influence of the type and amount of dietary fiber on exocrine pancreatic secretion. Four isonitrogenous diets were fed to each pig: W (whole wheat); WBS (whole wheat, wheat bran, wheat starch); WFS (whole wheat, wheat flour, wheat starch); and FC (wheat flour, wood cellulose). Wheat and wheat fractions came from the same batch of wheat. Crude fiber and dietary fiber (nonstarch polysaccharide) contents of diets W, WBS, WFS and FC (g/kg), respectively, were 40.8, 101.8; 63.7, 201.2; 20.5, 50.3; and 39.0, 60.7. Mean volumes of pancreatic juice (mL/24 h) for diets W, WBS, WFS and FC, respectively, were 4108, 4560, 2556 and 1757. Total enzymic and electrolyte concentrations were not significantly affected by diet changes, but mean protein and amylase outputs were lower for diet FC than for the others. It was concluded that the principal effect of increasing the dietary fiber content of the diets was to increase the volume of pancreatic juice and that this may have been due to noncellulosic components of the dietary fiber.

Beta-Adrenergic Inhibition of Pancreatic Secretion in Dogs

Terbutaline, a beta-adrenergic agonist, administered subcutaneously inhibits pancreatic exocrine secretion. We studied the effects of intravenous terbutaline and propranolol on cholecystokinin-stimulated pancreatic secretion in conscious dogs. Terbutaline inhibited pancreatic juice volume, bicarbonate concentration, bicarbonate output and protein output, but had no effect on protein concentration. Propranolol blocked this inhibition and had no effect on the response to cholecystokinin. These observations suggest that (1) terbutaline inhibits pancreatic secretion by a beta-adrenergic mechanism and (2) the primary effect of terbutaline on canine exocrine pancreas is inhibition of water and bicarbonate secretion.

Insulin and the parasympathetic dependence of pancreatic juice secretion in healthy and alloxan diabetic sheep.

Pancreatic function was measured in four ewes following vagal stimulation under control conditions and after the induction of alloxan diabetes. The volume and protein content of the pancreatic juice was measured along with simultaneous measurement of blood glucose and plasma insulin. The volume of pancreatic juice and its protein content decreased markedly in the diabetic state and returned to the initial value after insulin treatment. In normal animals, vagal stimulation markedly increased; the volume of pancreatic secretion and its protein content as well as the plasma insulin concentration. In the diabetic animals vagal stimulation caused only a slight increase in the protein content of pancreatic juice and plasma insulin concentration. It is suggested that insulin is probably one of the more important factors directly regulating the secretion of pancreatic juice.

Characteristics of Inhibition of Pancreatic Secretion by the β-Adrenergic Agonist, Terbutaline

This study was performed to characterize the inhibitory effects of terbutaline on pancreatic secretion. In experiments with pancreatic fistula dogs, intravenously administered terbutaline significantly reduced pancreatic juice volume, bicarbonate concentration, bicarbonate output, and protein output evoked by secretin or the octapeptide of cholecystokinin but had no effect on protein concentration. Subcutaneously administered terbutaline significantly reduced meal-stimulated pancreatic juice volume, bicarbonate concentration, bicarbonate output, and protein output and increased protein concentration in a dose-related manner. In other experiments, terbutaline had no effect on amylase release from dispersed guinea pig pancreatic acini. These observations suggest that the primary effect of terbutaline on the in vivo exocrine pancreas is inhibition of water and bicarbonate secretion; reduced output of pancreatic protein may be secondary to decreased flow of pancreatic juice.

Segmental Pancreatic Transplantation in Stockholm

Fifty-nine pancreatic transplantations have been performed at Huddinge Hospital between May 1974 and October 1985 with a substantial improvement in results over the years. In the most recent series, consisting of 19 combined renal and pancreatic transplantations performed May 1984 to September 1985; the 1-year actuarial patient survival and pancreatic graft survival were 86% and 66% respectively. Thirteen of these grafts are functional presently, at 18 to 2 months, and all such patients are insulin free and exhibit normal metabolic control. Our practice includes drainage of the pancreatic juice to the exterior by means of a pancreatic duct catheter during the first 2-3 postoperative weeks, thereby promoting healing of the pancreatico-enteric anastomosis. Although cold ischemia time was kept low in this series, a moderate graft pancreatitis developed, with a peak serum amylase level of 16.8 + 2.2 ukat/l and a peak amylase activity in the peripancreatic fluid of 280 + 110 ukat/l. The volume of pancreatic juice from the ductal catheter was very low in the first postoperative days but then rose to reach a plateau level of about 500 ml/day. The amylase activity in this juice was very high (9100 + 2500 ukat/l) during the first postoperative day, but then gradually decreased to reach a steady level around 3000 ukat/l after 4-7 days.

A new technique for chronic pancreatic cannulation in rats.

A new type of chronic pancreatic cannula is intended for examination of pancreatic exocrine secretion in conscious rats moving freely in their cages between the experiments. The recirculation of pancreatic juice and the free flow of bile into the duodenum is ensured. The pancreatic juice volume, protein output, amylase activity, and bicarbonate output were significantly higher in the chronically cannulated conscious rats than in the acutely anaesthetized cannulated rats. Advantages of the new cannula and the cannulation technique are described.

Short-term (8-day) effects of a raw soybean diet on exocrine pancreatic secretion and plasma gastrointestinal hormone levels in the pig.

The aim of the present study was to investigate the short-term (8-day) effects of feeding a raw soybean diet on exocrine pancreatic secretion and the plasma levels of gastrointestinal hormones in pigs. After adaptation to a heated soybean diet, 6 pigs (36.5 +/- 0.8 kg) were fitted with permanent fistulae of the pancreatic duct, the duodenum and a carotid artery. After post-surgical recovery of 8 days, the animals were submitted to two experimental periods, a 4-day period during which they were fed the heated soybean diet and an 8-day period during which they received the raw soybean diet. Exocrine pancreatic secretion and plasma levels of secretin, cholecystokinin, VIP, PP, somatostatin and gastrin were monitored each day of the two experimental periods. On the first day of raw soybean ingestion and till its end, the daily volume of pancreatic juice was higher than the mean volume measured during heated soybean ingestion. On the contrary, daily total protein output was unchanged. Specific activities of chymotrypsin, amylase and lipase were not modified by the raw soybean diet whereas, from the third day of the experimental period, that of trypsin was higher than the corresponding mean value determined during the first experimental period. Plasma levels of secretin and VIP were higher throughout raw soybean ingestion than the corresponding mean levels determined during the first experimental period. The plasma level of cholecystokinin increased only slightly and in the first days of the second experimental period only. The other gastrointestinal hormones studied were slightly (gastrin) or not (somatostatin, PP) affected by raw soybean feeding. It is suggested that feedback control of exocrine pancreatic secretion in pigs was the mechanism involved in the increase of pancreatic juice observed when raw soybean was fed. This volume increase would result from secretin release into the blood.

New analogues of secretin

For the evaluation of structure/activity relationships, some porcine secretin analogues, modified in the N-terminus, have been synthesized by segment condensation in solution. The secretin activity of the analogues was defined as the volume of pancreatic juice secreted in rats and dogs. The exchange of the N-terminal pentapeptide for the N-terminal pentapeptide of human somatotropin releasing factor (h-SRF) resulted in a peptide ([1-Tyr,2,4-Di-Ala,5-Ile]secretin) with practically no SRF-activity (less than 1% SRF-activity up to 100 μg/kg in the rat), but surprisingly high secretin activity (almost 100% in the rat, but only 1150 CU/mg (27%) in the dog). [3-L-Cysteic acid]secretin showed 1750 CU/mg (39%) in the dog, but a less activity (23%) in the rat. [6-D-Phe]secretin and [5-D-allo-Thr]secretin are again strongly species specific. They exhibited an activity of less than 1% in the dog, but about 10–15% in the rat. The smallest secretin activity was observed with [1-Cys,6-Cys]secretin in the oxidized form. The activity in the rat with this analogue was only about 0.2%.

Effect of synthetic neuromedin C, a decapeptide of gastrin-releasing peptide (GRP [18–27]), on blood flow and exocrine secretion of the pancreas in dogs

Neuromedin C, the smaller molecular form of gastrin releasing peptide (GRP [18–27]), has been recently identified from canine intestinal muscle and porcine spinal cord. This study was conducted to determine if this newly identified peptide retains biological activity on canine pancreas in vivo. Intravenous injection of graded doses of synthetic Neuromedin C caused a marked increase of systematic blood pressure and initial reduction of pancreatic blood flow in eleven anesthetized dogs, as measured by Laser Doppler Flowmetry. Flow volume and protein output of pancreatic juice were also increased by Neuromedin C in a dose-related manner in six dogs. These results suggest that this peptide is one of the biologically active forms of mammalian bombesin-like peptides and may possess physiological significance as a novel neuropeptide.

PERMANENT RE-ENTRANT DIVERSION OF PORCINE PANCREATIC SECRETIONS

A surgical procedure was developed to permit improved long-term collection of exocrine pancreatic secretions. A cannula was used to conduct pancreatic juice from a small isolated segment of duodenum which received the pancreatic duct, through permanent intercostal fistulas, and back into the duodenum within 3 cm of the normal entry point for pancreatic juice. Success with this procedure is attributed to fistula location, one-way valve design of the re-entrant arm of the cannula and precautions taken to minimize the formation of intra-abdominal adhesions. Pancreatic juice was collected from three barrows (35 kg initial weight) which were fed three cornstarch-based diets (high fat — 14% crude protein, 10% tallow; control — 14% crude protein, 2% tallow; protein-free — 0% crude protein, 2% tallow), twice daily, 0.9 kg each meal, 12 h apart for a 2-wk period. The daily volume of pancreatic juice secreted was 3.9, 4.0 and 3.5 L (n = 6) for the high fat, control and protein-free diets, respectively. In the same order for the diets, the daily protein secretion was 15.3, 15.0 and 12.2 g respectively. A 12-h secretion profile related to meal time showed a similar response pattern to feeding for all diets, i. e., secretion rates increased within the first 3 h, peaked during 3–7 h and decreased to basal rates during the last 5 h. Secretion rates obtained from blind 5-cm duodenal pouches did not exceed 20 mL per 24 h. During the 4-mo study, pancreatic secretions were persistent and meal induced secretion patterns were sustained. Cannulas were still functional when pigs achieved liveweights greater than 100 kg. Key words: Cannulation, pancreas, swine

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)

EFFECT OF SECRETAGOCUES ON PANCREATIC EXOCRINE SECRETION IN THE MONKEY AND THE DOG

The effects of secretin, cholecystokinin, dopamine, histamine and acetylcholine on the secretion of pancreatic juice were investigated in the monkey and the dog. In the resting state, bicarbonate concentration and the volume of pancreatic juice in the monkey were greater than those in the dog. However, the protein concentration of pancreatic juice in the monkey was less than that in the dog. Intravenous administration of secretin, cholecystokinin, histamine and acetylcholine caused a dose dependent increase in pancreatic secretion in both species. The responses in the monkey were greater than those in the dog. Dopamine caused pancreatic secretion only in the dog. The increase in bicarbonate concentrations of pancreatic juice induced by secretin and histamine in the monkey were greater than that in the dog. Increase in protein concentrations of the juice induced by cholecystokinin and acetylcholine in the monkey were less than that in the dog. However, pancreatic juice pH in both species was the same and was not affected by the secretagogues in the resting state or during the stimulation by secretogogues. From these results, it is concluded that there is a species difference in the secretory actions of the secretagogues in the monkey and the dog.

Inhibition of Pancreatic Secretory and Trophic Response to Caerulein by the H<sub>2</sub>-Receptor Antagonist Ranitidine in the Rat

The effect of ranitidine (20 mg . kg-1) and cimetidine (50 mg . kg-1) on pancreatic secretory and trophic responses to caerulein (1 microgram . kg-1) was studied in the rat. Ranitidine or cimetidine were administered alone or combined with caerulein twice a day for 7 days. Saline-treated rats were used as controls. At the end of treatment animals were anesthetized and pancreatic juice was collected for 1 h after intravenous secretin plus CCK-PZ (8 U . kg-1). Afterwards rats were sacrificed and growth and composition of pancreatic tissue were determined. Compared with control (saline) values, volume of pancreatic juice and output of trypsin and amylase were increased by treatment with caerulein. Ranitidine, when given combined with caerulein, completely abolished the secretory response induced by the peptide, whereas it was totally ineffective when given alone. Cimetidine (alone or combined with caerulein) was always ineffective. Caerulein increased pancreatic weight, total pancreatic trypsin, amylase and RNA content. Here again ranitidine, combined with caerulein, abolished almost completely the trophic effect of caerulein on the pancreas, but when given alone it did not influence pancreatic growth and composition. Also in this case, cimetidine was completely inactive. These results suggest that ranitidine affects exocrine pancreas with an action independent of the H2-receptor blockade.

New analogues of secretin

Abstract For the evaluation of structure/activity relationships, some porcine secretin analogues, modified in the N-terminus, have been synthesized by segment condensation in solution. The secretin activity of the analogues was defined as the volume of pancreatic juice secreted in rats and dogs. The exchange of the N-terminal pentapeptide for the N-terminal pentapeptide of human somatotropin releasing factor (h-SRF) resulted in a peptide ([1-Tyr,2,4-Di-Ala,5-Ile]secretin) with practically no SRF-activity (less than 1% SRF-activity up to 100 μg/kg in the rat), but surprisingly high secretin activity (almost 100% in the rat, but only 1150 CU/mg (27%) in the dog). [3-L-Cysteic acid]secretin showed 1750 CU/mg (39%) in the dog, but a less activity (23%) in the rat. [6-D-Phe]secretin and [5-D-allo-Thr]secretin are again strongly species specific. They exhibited an activity of less than 1% in the dog, but about 10–15% in the rat. The smallest secretin activity was observed with [1-Cys,6-Cys]secretin in the oxidized form. The activity in the rat with this analogue was only about 0.2%.

The dependence of exocrine pancreatic secretion on insulin in sheep.

Exocrine pancreatic secretion, blood insulin, glucose and free fatty acid concentrations were measured on days 1, 4 and 5 of a 5 d experimental period. Sheep were treated with alloxan (day 2) and insulin (day 5). The volume of pancreatic juice decreased markedly in the diabetic state and returned to the initial value after insulin treatment. The daily secretion of lipase and amylase decreased during development of diabetes. Injection of insulin restored the secretion of lipase but not amylase. It is suggested that insulin potentiates the stimulatory action of the vagus nerve on the pancreatic secretion of sheep.

Effect of partial exclusion of pancreatic juice on rat basal pancreatic secretion

Experiments were conducted to determine the relationship between the percentage of pancreatic secretion diverted from the intestine and pancreatic exocrine secretion in conscious rats. Rats with cannulas draining bile and pancreatic juice had increasing percentages (0%–100%) of their pancreatic secretion diverted from the intestine while all bile was returned. Stimulation of pancreatic protein and fluid output by diversion of pancreatic juice from the intestine did not occur if 10% of the volume of pancreatic juice secreted was returned to the intestine. Return of 5% of pancreatic secretion reduced the pancreatic protein response by half (compared with complete diversion). The results are interpreted as evidence for a threshold in negative feedback regulation by luminal proteases whereby increased pancreatic secretion does not occur until luminal protease activity is reduced by >90%. The results also suggest that inhibition of pancreatic secretion by proteases in pancreatic juice is far more effective than inhibition by proteases (e.g., trypsin) infused singly.

Effect of atropine on rat basal pancreatic secretion during return or diversion of bile-pancreatic juice.

The effect of atropine on basal pancreatic exocrine secretion in conscious rats was determined with and without return of bile-pancreatic juice (BPJ) to the intestine. Rats were prepared with cannulas draining bile and pancreatic juice separately and with duodenal cannulas for return of secretions. Experiments were begun 3 days postoperatively. During continuous return of bile-pancreatic secretions, intravenous atropine (100 micrograms/kg-hr) caused a sustained 80-90% inhibition of pancreatic protein secretion, with a much smaller suppressive effect on pancreatic juice volume. Diversion of bile-pancreatic juice from the intestine markedly increased pancreatic protein and fluid secretion in control and atropine-infused rats, but the response was significantly inhibited by atropine (volume 31% inhibition, protein output 41% inhibition). The results indicate that basal pancreatic protein secretion during return of BPJ is largely maintained by cholinergic influence, possibly due to an enteropancreatic reflex, and that the inhibition of the pancreatic response to acute diversion of BPJ by atropine is probably secondary to inhibition of gastric secretion.