Effects of pancreatic polypeptide on biliary flow and bile acid secretion stimulated by secretin and cholecystokinin in the conscious pig

Fourteen castrated male Large White pigs, weighing 42.5 +/- 1.0 kg, were fitted with biliary and duodenal fistulae for biliary secretion studies. Furthermore, catheters were placed in a carotid artery for blood sampling and in a jugular vein for peptide infusion. Bile was automatically restituted to the animals and continuously sampled for analysis on experimental days. Following an 8 day recovery period, infusion studies were performed after an overnight fast. After a 30 min basal period, sustained biliary flow and bile acid output were obtained and maintained throughout the assay with secretin (36 pmol/kg/h) and CCK-8 (600 pmol/kg/h) infusion. Then, 200, 400, 600, 800 or 1200 pmol/kg/h of porcine pancreatic polypeptide (PP) were infused for 60 min. Secretin plus CCK infusion was continued for 1 h after PP infusion was stopped. Each dose of PP was given on a separate day. Biliary flow was not affected by PP except for the dose of 400 pmol/kg/h. On the contrary, bile acid concentration and output decreased with the lowest dose of PP (200 pmol/kg/h). As soon as the first dose of PP was infused, bile acid concentration and output fell to about 60% of values obtained with secretin plus CCK. Plasma levels of PP were below or similar to postprandial values for 200, 400 and 600 pmol/kg/h and they were significantly larger with 800 and 1200 pmol/kg/h. Bile acid concentration and output did not return to values obtained with secretin plus CCK infusion after cessation of PP infusion. In conclusion, porcine PP given in physiological doses to the pig decreases bile acid output whereas biliary flow remains unaffected.     

Effect of acute hyperglycemia on basal, secretin and secretin + cholecystokinin stimulated exocrine pancreatic secretion in humans

Pancreatico-biliary secretion is reduced during acute hyperglycemia. We investigated whether alterations in pancreatico-biliary flow or volume output are responsible for the observed reduction in duodenal output of pancreatic enzymes and bilirubin during hyperglycemia. Eight healthy subjects were studied on two occasions during normoglycemia and hyperglycemia (15 mmol/l). Pancreatico-biliary output was measured by aspiration using a recovery marker under basal conditions (60 min), during secretin infusion (0.1 CU/kg.h) for 60 min and during secretin + CCK (0.5 IDU/kg.h) infusion for 60 min. Secretin was infused to stimulate pancreatico-biliary flow and volume output. Secretin significantly (P<0.005-P<0.05) increased volume and bicarbonate output and CCK significantly (P<0.01) increased the output of bilirubin, pancreatic enzymes, bicarbonate and volume, both during normoglycemia and hyperglycemia. During hyperglycemia basal, secretin stimulated and secretin + CCK stimulated total pancreatico-biliary output were significantly (P<0.005-P<0.05) reduced compared to normoglycemia. The incremental outputs, however, were not significantly different between hyper- and normoglycemia. Pancreatic volume output was significantly (P<0.05) reduced during hyperglycemia compared to normoglycemia under basal conditions (31+/-16 m/h versus 132+/-33 m/h) during secretin infusion (130+/-17 ml/h versus 200+/-34 m/h) and during secretin + CCK infusion (370+/-39 ml/h versus 573+/-82 ml/h). Plasma PP levels were significantly (P<0.05) reduced during hyperglycemia. It is concluded that 1) hyperglycemia significantly reduces basal pancreatico-biliary output 2) the incremental pancreaticobiliary output in response to secretin or secretin + CCK infusion is not significantly affected during hyperglycemia, 3) a reduction in volume output contributes to the inhibitory effect of hyperglycemia on pancreatico-biliary secretion, 4) hyperglycemia reduces PP secretion suggesting vagal-cholinergic inhibition of pancreatico-biliary secretion and volume during hyperglycemia.     

Effects of cholecystokinin octapeptide on the pancreatic exocrine secretion in the pig

In conscious pigs, intravenous infusion of serial doses of cholecystokinin octapeptide (CCK8; 2.9-232.3 pmol.kg-1.min-1) upon a background of secretin resulted in a linear increase of plasma CCK-like immunoreactivity (CCK-LI) concentration and evoked a dose-related increase of pancreatic volume and bicarbonate and protein outputs. The threshold plasma CCK-LI concentration for significant pancreatic response was 103.8 +/- 10.2 pM using a CCK8 dose of 8.8 pmol.kg-1.min-1. The maximum pancreatic response was observed for a plasma CCK-LI level of 498.0 +/- 15.3 pM using 77.2 pmol CCK8.kg-1.min-1. In anesthetized pigs, the threshold plasma CCK-LI concentration for pancreatic response was 1500 pM (actual CCK8 dose of 60.3 pmol.kg-1.min-1). The physiological relevance of this finding was assessed by comparing the food-induced increase of pancreatic secretion with that of plasma CCK-LI. Food ingestion was followed by a sharp pancreatic response and by a progressive increase of plasma CCK-LI to a peak increment of about 15 pM. Gel chromatography of portal and peripheral plasma from fed animals revealed three major peaks in the volumes of CCK33/39 and CCK8, and in a volume intermediate between CCK33/39 and CCK8. An additional minor component eluted ahead of CCK33/39. CCK8, which is one of the CCK components released after food intake, appears to be a fairly weak pancreatic stimulant in pigs.     

Inhibitory effect of pancreastatin on pancreatic exocrine secretion in the conscious rat

The effect of newly discovered pancreastatin on pancreatic secretion stimulated by a diversion of bile-pancreatic juice (BPJ) from the intestine was examined in the conscious rat. Exogenous pancreastatin infusion (20, 100 and 200 pmol/kg.h) inhibited pancreatic protein and fluid outputs during BPJ diversion in a dose-dependent manner. Pancreastatin did not affect plasma cholecystokinin (CCK) concentrations. Pancreastatin (100 pmol/kg.h) inhibited CCK-stimulated pancreatic secretion, but did not inhibit secretin-stimulated pancreatic secretion. Pancreastatin alone, however, did not affect basal pancreatic secretion. In contrast, pancreastatin (10(-10)-10(-7)M) did not suppress CCK-stimulated amylase release from isolated rat pancreatic acini. These results indicate that pancreastatin has an inhibitory action on exocrine function of the pancreas. This action may not be mediated by direct mechanisms and nor via an inhibition of CCK release. It is suggested that pancreastatin may play a role in the regulation of the intestinal phase of exocrine pancreatic secretion.     

Effect of colonic distension on exocrine pancreatic secretion of the conscious rat

In the conscious rat the increasing distension of the colon (from 2 to 6 ml) induced a slight decrease of exocrine pancreatic secretion which was more important for protein output than for volume. Nevertheless this inhibitory effect was never significant even with the important distension of 6 ml which induced a visible uneasiness in the animal.     

Comparative effects of vasoactive intestinal peptide and secretin on exocrine pancreatic secretion in the cat

The stimulatory effect of vasoactive intestinal peptide (VIP) and secretin has been compared on exocrine pancreatic secretion in anaesthetized cats. Both peptides were given by bolus intravenous injection and continuous intravenous infusion. After bolus injection, VIP stimulated pancreatic secretion only weakly. On the contrary, during intravenous infusion, the maximal effect of VIP did not differ significantly from that of secretin. Therefore, while the potency of VIP is always lower than that of secretin, its efficacy appears to be strictly dependent on the mode of administration.     

Effects of somatostatin on pancreatic exocrine function. Interaction with secretin.

The release of hydrolases from rat pancreas was stimulated in vivo and in vitro by somatostatin. In vitro this hypersecretion was accompanied by a moderate but significant rise in intracellular cyclic AMP. In addition, the tetradecapeptide inhibited rises of cyclic AMP provoked by secretin. The existence of the same sequence of four amino acid residues in the two peptides suggests that somatostatin's activation of the exocrine pancreas depends on its interaction with secretin receptors.     

Effect of somatostatin on exocrine pancreatic secretion stimulated by pancreozymin-secretin or by a test meal in the dog

In 4 dogs with chronic duodenal and gastric fistulae, exocrine pancreatic function was assessed by cannulating the pancreatic duct and collecting the duodenal contents. Both methods were applied in each animal. Pancreatic secretion was stimulated by infusion of 2 CHR units of pancreozymin and secretin or by administration of a liquid test meal, injected into the stomach through the gastric fistula. During both experiments 3.5 microgram/kg somatostatin was given as bolus injection followed by an infusion of 3.5 microgram/kg/h. Somatostatin caused a significant reduction in protein and amylase output and in the bicarbonate concentration during stimulation with pancreozymin-secretin. Volume and bicarbonate slightly decreased but not to a significant extent. Duodenal volume and the duodenal activities of trypsin and amylase were significantly reduced during test meal stimulation and somatostatin infusion. Somatostatin is a potent inhibitor of exocrine pancreatic function mainly influencing enzyme secretion.     

Surgical preparation for the study of pancreatic exocrine secretion in the conscious preruminant goat

A new surgical procedure for the study of pancreatic secretion in the conscious preruminant goat, under conditions which approach physiological normality, is described. The bile and pancreatic juice retain their natural route and preserve the normal function of the sphincter of Oddi. Experiments could be started 3 days after surgery.     

Effect of pituitary adenylate cyclase activating polypeptide on rat pancreatic exocrine secretion.

A novel neuropeptide, pituitary adenylate cyclase activating polypeptide (PACAP), which has been isolated from ovine hypothalami, shows 68% homology with vasoactive intestinal peptide (VIP). Since VIP stimulates amylase secretion from the pancreas, we investigated the effect of PACAP and VIP on rat pancreatic exocrine secretion after intravenous injections of PACAP-27, PACAP-38, or VIP at doses of 2.5, 5 or 10 nmol/kg. Results showed: 1) Bolus injection of PACAP stimulated pancreatic amylase and protein secretions in a dose-dependent manner; and 2) Stimulation of amylase secretion with 10 nmol/kg of PACAP-27 was greater than that induced with the same dose of VIP or PACAP-38 (p less than 0.05).     

Basal and spontaneous exocrine pancreatic secretion in conscious and anaesthetized chickens, Gallus domesticus

Basal exocrine pancreatic secretion was studied in anaesthetized and conscious chickens and spontaneous secretion was studied in anaesthetized chickens. Results are compared with those of other vertebrates to estimate the specific pattern of this secretion in birds. The flow of pancreatic juice was greater in conscious chickens than when anaesthetized (Table 1). Amylase activity was greater than that of the other species and was of the same order in anaesthetized and conscious birds (Table 1). A spontaneous exocrine pancreatic secretion was seen to remain after eliminating a large part of the tonic influences (Table 2).     

Influence of cholecystokinin, vasoactive intestinal peptide and secretin on plasma concentration of avian pancreatic polypeptide in laying hens

The influence of saline infusion (i.v.) followed by infusion of either cholecystokinin, vasoactive intestinal peptide, or secretin on plasma concentration of avian pancreatic polypeptide (aPP) was studied in sixteen 18-26-week old Single Comb White Leghorn hens. Three concentrations were used for each hormone. Blood was drawn after both saline and hormone infusions and assayed for aPP content. No significant influence of any of the three hormones on plasma aPP level was found in either fed or fasted hens.     

The influence of cholecystokinin, vasoactive intestinal peptide and secretin on pancreatic and biliary secretion in laying hens

White Leghorn hens, 14-29 weeks old, were surgically fitted with cannulas for collecting pancreatic and biliary secretions, and a jugular cannula for continuous infusion of either cholecystokinin (CCK), vasoactive intestinal peptide (VIP), or secretin. As compared to secretory levels during saline infusion, CCK significantly stimulated biliary flow and biliverdin concentration in bile; VIP significantly depressed biliverdin concentration but enhanced bicarbonate secretion in both pancreatic and biliary secretions, and also increased total pancreatic flow. Secretin depressed biliary flow and increased pancreatic bicarbonate release. The principal hormonal regulator of biliary secretion appears to be CCK, and that of pancreatic secretion to be VIP.     

The influence of potato fibre on exocrine pancreatic secretions and on plasma levels of insulin,secretin and cholecystokinin in growing pigs

The effect of a potato fibre preparation on exocrine pancreatic secretions and on gastrointestinal hormone levels in plasma was studied in three 8 weeks old piglets that were surgically fitted with a jugular vein catheter for blood sampling, a pancreatic duct catheter and a T‐shaped duodenal cannula for collection of pancreatic juice. The animals were fed for 2 weeks a control diet (experimental period 1), thereafter for 2 weeks the control diet supplemented with 2% potato fibre (experimental period 2) and for another 2 weeks the control diet again (experimental period 3). Additionally, intraduodenal (i.d.) infusions of the experimental diet, the control diet and potato fibre as well as i.v. infusions of a solution containing cholecystokinin (CCK) and secretin were administered.

Potato fibre in the diet evoked in tendency an increase in the volume of secretion of pancreatic juice and a significant increase both in the mean values of the total protein content and total activities of lipase, trypsin and a‐amylase when compared to the control diet. The i.d. infusion of the control diet, experimental diet and fibre infusate as well as the i.V. administration of the hormone infusate led to a spontaneous secretory response of the exocrine pancreas. Besides gastrointestinal hormones, such as CCK, other factors such as short chain fatty acids may be involved in the regulation of the exocrine pancreas.     

Effects of parathyroid hormone on exocrine pancreatic secretion in parathyroidectomized dogs

The effects of intravenous parathyroid hormone (PTH) on steady state Secretin-induced pancreatic secretion were studied in seven dogs before and after parathyroidectomy. Free flow of pancreatic juice was obtained by direct cannulation of the main pancreatic duct (the minor duct being ligated) : a gastric fistula prevented the entry of gastric acid into the duodenum. In the normal dog PTH caused a significant increase in volume and bicarbonate concentration, reciprocal change in chloride and no change in total protein concentration. The stimulatory effect of PTH was dose-dependent. In the parathyroidectomized dog, the basic Secretin-induced secretion was lower than the preoperative values, but PTH infusion caused a significant increase in volume of fluids and bicarbonate concentration, reciprocal change in chloride and no change in protein concentration. These results were not dependent on calcium blood level, and did not change after calcium injection to the hypocalcemic parathyroidectomized dog. It is suggested, that PTH may have a direct effect on pancreatic exocrine secretion.     

Effects of pancreastatin on insulin and pancreatic polypeptide secretion in the dog

Porcine pancreastatin (1.19 nmol) was administered into the peripheral vein (i.v.) or the third cerebral ventricle (i.t.v.) of dogs and its effect on the secretion of insulin and pancreatic polypeptide (PP) studied. Neither means of administration had any effect on basal and glucose-induced insulin or PP secretion. However, i.v. pancreastatin did inhibit the i.v. CCK-8-induced insulin but not PP release. Pancreastatin may thus play a role in the regulation of insulin secretion in the canine pancreas.     

The effect of oxyntomodulin (Glucagon-37) and glucagon on exocrine pancreatic secretion in the conscious rat

The inhibitory effect of glucagon on exocrine pancreas has been the subject of controversial reports. On the other hand, oxyntomodulin (bioactive enteroglucagon or glucagon-37), a 37 amino acid peptide isolated from porcine lower intestine, has been shown to be 10–20 times more potent than glucagon in inhibiting gastric acid secretion in the rat. In view of this, the effect of glucagon and oxyntomodulin on basal and caerulein-stimulated pancreatic secretion has been studied, during re-introduction of pancreatic juice into duodenum, in the conscious rat provided with pancreatic and duodenal fistulas. A depression of pancreatic function was observed with both peptides on the three parameters studied: (volume of juice secreted, bicarbonate and protein output), either under basal conditions or during stimulation by caerulein. In all the experimental conditions used, oxyntomodulin was ca. ten times more potent than glucagon in its inhibitory effect. The fact that oxyntomodulin, as what is observed in the stomach, is one order of magnitude more potent than glucagon in inhibiting pancreatic secretion suggests that the biological mechanisms by which the peptides of the glucagon-family act on exocrine pancreas are similar, or related to that present at the gastric level.