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C Beglinger

Publications and source records attributed to C Beglinger.

At least 73 records · Page 4Linked to original sources
PubMed1988

Mechanisms of terbutaline-induced inhibition of exocrine pancreatic secretion in humans.

Terbutaline, a selective beta 2-adrenoreceptor agonist, has recently been advocated as a potential agent for treating patients with pancreatic fistulae. In the present study, we attempted to quantify the presumed effects of terbutaline on exocrine pancreatic secretion in humans and to characterize possible mechanisms of action. In six healthy volunteers, the pancreas was stimulated by infusion of graded doses of secretin (15.5-250 ng/kg/h) or by infusion of secretin (15.5 ng/kg/h) plus graded doses of caerulein (3.3-30 ng/kg/h). The experiments were repeated in each subject without and with administration of terbutaline. Pancreatic secretion was assessed by a marker perfusion technique and plasma somatostatin and pancreatic polypeptide (PP) levels by radioimmunoassay. Terbutaline had no significant effect on secretin-stimulated pancreatic secretion, but significantly inhibited caerulein-stimulated pancreatic fluid secretion and trypsin output. Plasma somatostatin and PP levels were not affected by terbutaline. The inhibitory effect required the administration of pharmacologically large doses of terbutaline. We conclude that the weak inhibitory effect of terbutaline on exocrine pancreatic secretion is not mediated via somatostatin nor PP and that our data do not support a major role for beta-adrenergic mechanism as regulator of pancreatic secretion.

Adult↗
PubMed1988

Stimulation of pancreatic secretion in man by a protease inhibitor (camostate).

Pancreatic secretion and plasma cholecystokinin (CCK) and secretin levels were measured in 10 healthy volunteers after application of a serine protease inhibitor (camostate) to study the mechanism of feedback regulation. Camostate produced a strong inhibition of trypsin and chymotrypsin activity in duodenal juice for 1 h. This was accompanied by an increase in duodenal aspirate volume and pancreatic enzyme secretion under both basal and secretin-stimulated conditions. Due to inhibition of tryptic activity, survival of lipase activity in duodenal juice was prolonged. In control experiments we ruled out that the volume and the pH of the solution were responsible for stimulation of pancreatic secretion. The protease inhibitor did not alter pancreatic secretion, which was stimulated by a test meal. Plasma levels of CCK and secretin were not changed after duodenal perfusion of camostate. These observations suggest that trypsin and chymotrypsin are involved in feedback regulation of pancreatic secretion in man which is, however, not mediated by CCK or secretin.

Cholecystokinin↗
PubMed1988

Effect of calcitonin and calcitonin gene-related peptide on pancreatic functions in man.

Calcitonin gene-related peptide (CGRP) has recently been identified in central and peripheral nerve fibres, including those of blood vessels supplying the exocrine pancreas, and in pancreatic islet cells. Moreover, receptors have been characterised in the same tissue. The present study examined the effects of human CGRP and of calcitonin on exocrine pancreatic secretion and on islet cell function in nine healthy volunteers. CGRP (300 ng/kg/h) caused, respectively, a 25% and 31% inhibition of caerulein stimulated trypsin and amylase output which was similar to that seen with calcitonin (300 ng/kg/h). Arginine stimulated insulin and glucagon release was unaffected by either CGRP, or calcitonin. Calcitonin gene-related peptide caused cutaneous flushing, but did not affect the pulse rate or arterial blood pressure in the doses tested. Calcitonin gene-related peptide inhibits exocrine pancreatic secretion in vivo in man, but does not affect islet cell hormone release.

Adult↗
PubMed1988

Pancreatic bicarbonate response to HCl before and after cutting the extrinsic nerves of the pancreas in dogs.

In two sets of dogs with gastric and pancreatic fistulas, we studied the effect of atropine on pancreatic bicarbonate output and release of secretin in response to intraduodenal HCl before and after stepwise removal of the extrinsic nerves of the pancreas, i.e., celiac and superior mesenteric ganglionectomy alone or truncal vagotomy alone and truncal vagotomy plus celiac and superior mesenteric ganglionectomy. Ganglionectomy alone did not alter the incremental bicarbonate response to HCl. Truncal vagotomy alone significantly (P less than 0.05) decreased the incremental bicarbonate response to low (1.5 and 3 mmol/h) but not high (6 to 24 mmol/h) loads of HCl. Additional ganglionectomy restored the bicarbonate response to prevagotomy levels. With the extrinsic nerves intact and after ganglionectomy, but not after truncal vagotomy and truncal vagotomy plus ganglionectomy, intravenous atropine (14 nmol.kg-1.h-1) significantly reduced the incremental bicarbonate response to low (1.5 and 3 mmol/h) but not high loads of HCl. Neither the different surgical procedures nor atropine significantly altered plasma levels of secretin basally and in response to intestinal HCl. We conclude that 1) cholinergic fibers within the vagus nerves but not the splanchnic nerves are important mediators of the pancreatic bicarbonate response to low loads of HCl and 2) release of secretin by intestinal HCl is not under cholinergic and splanchnic control.

Animals↗
PubMed1988

Release of secretin along the canine small intestine.

The profile of secretin release along the entire canine small intestine was examined in this study. Four equal loops of the small gut, from the duodenal bulb to the ileocoecal valve, were isolated. In eight anesthetized dogs the four segments were perfused for 40 min each in random order with an acidified (pH 2.5) emulsion of 20 mM oleic acid. In four dogs control experiments were performed using 0.15 M saline. Secretin release in portal venous blood was measured by a sensitive radioimmunoassay. Although secretin was mainly released in the first quarter of the small intestine (310 pM X 40 min), large amounts of secretin, 33% of the total secretin release, were liberated in the second quarter of the small intestine (164 pM X 40 min). Minute amounts of secretin (23 pM X 40 min) were released in the third quarter, whereas perfusion of the last quarter of the small gut failed to release secretin. We conclude that the major portion of secretin is releasable in the first quarter of the small gut. High amounts of secretin can be liberated in the second quarter of intestine, an area that is probably never exposed to pH below 4.5 (the known threshold for secretin release by acid), but is still exposed to fatty acids (other releasers of secretin).

Animals↗
PubMed1988

Reduction in early recurrence of variceal bleeding by propranolol.

Survival after variceal bleeding depends greatly on the outcome of the immediate posthaemorrhagic period. This may in turn depend on the recurrence of bleeding. We therefore prospectively evaluated the influence of propranolol on the recurrence of variceal haemorrhage during the early period after the acute bleeding episode. Twenty consecutive patients with acute variceal haemorrhage and liver disease were randomly assigned to treatment either with propranolol or placebo orally for 14 days. Propranolol significantly decreased the rate of recurrence of variceal haemorrhage during this early period (p = 0.0028; 95% confidence interval in the placebo group, 90 +/- 20%; in the beta blocker group, 20 +/- 26%). Whereas a recurrence of variceal bleeding occurred in 9 of 10 patients in the placebo group, only 2 of 10 rebled during treatment with propranolol. These results suggest that propranolol may prevent rebleeding in the crucial early period after acute haemorrhage from oesophageal varices.

Acute Disease↗
PubMed1988

Human secretin. Biologic effects and plasma kinetics in humans.

The action of synthetic human secretin, which differs in two amino acid residues from porcine secretin, was compared with synthetic porcine secretin in 6 healthy volunteers. Pancreatic secretion was assessed by a marker perfusion technique and plasma secretin concentrations were assessed by a specific radioimmunoassay. Increasing doses of either human or porcine secretin produced increasing bicarbonate output (p less than 0.01), whereas trypsin and lipase were not stimulated over basal. The highest doses of secretin induced a significant increase in pancreatic amylase secretion. The two secretin preparations were found to be equipotent with respect to pancreatic secretion and plasma kinetics. Significant increases of plasma secretin were observed after a steak meal in 15 volunteers (p less than 0.001). When human secretin was infused at postprandial concentrations, significant increases in pancreatic bicarbonate output were observed (p less than 0.05). We conclude (a) that the substitution of two amino acids in human secretin does not affect biologic activity and plasma metabolism of the compound; (b) secretin does not stimulate pancreatic enzyme secretion at physiologic concentrations; and (c) the stimulatory effects of secretin on pancreatic amylase remain to be elucidated. The study suggests that human secretin is a true hormone.

Adult↗
PubMed1987

Biological effects of a proglumide derivative as cholecystokinin antagonist in conscious dogs.

In conscious dogs we studied the effects of a new cholecystokinin (CCK) antagonist (coded CR 1505) on CCK8-stimulated exocrine pancreatic secretion and release of pancreatic polypeptide (PP). Graded doses of CCK8 (25-400 ng kg-1h-1) were infused i.v. Experiments were repeated against a background infusion of CR 1505 at different doses (0.1, 1 and 10 mg kg-1h-1). The lowest dose of CR 1505 had no biological effects. However, at the upper two doses the compound significantly inhibited the CCK8-stimulated PP release. Furthermore, a significant inhibition of exocrine pancreatic protein secretion was observed with 10 mg kg-1h-1 of CR 1505 (P less than 0.05). The results suggest that CR 1505 could be a useful tool in defining the physiological role of CCK in vivo.

Animals↗
PubMed1987

Absorption of an aqueous solution of a new synthetic somatostatin analogue administered to man by gavage.

To determine the local gastrointestinal absorption of a new synthetic somatostatin analogue (SMS 201-995 = Sandostatin), an intestinal tube was passed in eight healthy volunteers and on different days an aqueous solution was administered at four different locations: stomach, proximal duodenum, ligament of Treitz and jejunum. In a follow-up study, an oro-ileal tube was passed in six of the original volunteers and the drug solution was administered in to the terminal ileum. The aqueous solution of SMS was rapidly absorbed from the gastrointestinal tract after local application, and it was well tolerated. Absorption of the drug from the different sites was comparable, although there was a tendency to decreased peptide absorption after ileal administration. Absorption of the drug was quite variable between the subjects and the different locations. The dose-corrected systemic availability relative to subcutaneous administration in another study was 0.28%. However, significant plasma SMS concentrations were achieved, suggesting that oral delivery of the polypeptide may eventually be possible for long-term treatment of a variety of disorders.

Adult↗
PubMed1987

Gastrin is not a physiological regulator of pancreatic exocrine secretion in the dog.

The role of gastrin as a regulator of exocrine pancreatic secretion has not been proven adequately. In the present study we therefore compared the relative molar potencies of sulfated and unsulfated gastrin 17 with structurally related CCK peptides (synthetic CCK-8 and natural porcine CCK-33) in stimulating exocrine pancreatic secretion in conscious dogs. Dose response curves were constructed for pancreatic and gastric acid secretion. Plasma gastrin levels after exogenous gastrin 17-I and -II were compared with postprandial gastrin concentrations (meal: ground beef 20 g/kg body wt). The molar potency estimates calculated with synthetic CCK8 as standard (potency = 1.00) for pancreatic protein secretion were natural porcine 50% pure CCK-33 1.60, gastrin 17-I 0.12, and gastrin 17-II 0.16. All four peptides induced a dose-dependent increase in pancreatic bicarbonate output. However, the blood concentrations needed to stimulate pancreatic secretion were above the postprandial gastrin levels. Our data indicate that both gastrin 17 peptides are not physiological regulators of pancreatic enzyme secretion in dogs.

Animals↗
PubMed1987

Circulating somatostatin. Physiological regulator of pancreatic function?

The present study was designed to determine whether somatostatin is released into the circulation in sufficient amounts to regulate exocrine and endocrine pancreatic function and to evaluate the possible role of somatostatin as a hormonal regulator of the pancreas. Mean plasma somatostatin levels (SLI) increased from 11 +/- 2 pmol liter-1 to peak concentrations of 18 +/- 2 in six healthy male volunteers after a steak meal (P less than 0.05). Infusion of somatostatin inhibited hormone-induced exocrine pancreatic secretion and suppressed cerulein-stimulated pancreatic polypeptide (PP) secretion, but did not significantly change arginine-stimulated insulin and glucagon release at mean plasma somatostatin concentrations within the range seen after a meal. The amount of somatostatin released after a meal thus was of sufficient magnitude to inhibit exocrine pancreatic function and PP release. On the other hand, basal and arginine-stimulated glucagon and insulin secretions were not significantly affected by these plasma concentrations of intravenous somatostatin suggesting that the exocrine pancreas might be more sensitive to somatostatin than the islet cells. We conclude that somatostatin in concentrations within the range seen after a meal is a potent inhibitor of stimulated acinar cell function in man. The findings support the hypothesis that somatostatin acts as a true hormonal regulator.

Adult↗
PubMed1986

Effect of a new somatostatin analogue on pancreatic function in healthy volunteers.

We studied the effect of four graded doses of SMS 201-995, a synthetic octapeptide somatostatin analogue (27, 80, 240, and 720 ng/kg/h) on the basal and secretin-plus-cerulein-stimulated exocrine pancreatic function and pancreatic polypeptide (PP) release in five healthy volunteers. Duodenal fluid secretion and bicarbonate output under basal and stimulated conditions were not significantly affected by any dose of SMS. The basal and stimulated enzyme secretion were decreased in a non-dose-dependent manner by all SMS doses used in the study and showed a 75% inhibition of the secretin-plus-cerulein-stimulated trypsin and amylase output. The cerulein-stimulated PP release was significantly suppressed by all four SMS doses. SMS appears to be a strong inhibitor of pancreatic enzyme secretion, at the same time affecting the PP release.

Adult↗
PubMed1986

Effect of circulating somatostatin on exocrine pancreatic secretion in conscious dogs.

We determined the effects of exogenous somatostatin-14 (100 and 200 ng/kg/h; mimicking postprandial somatostatin concentrations) on pancreatic responses to a background infusion of secretion in combination with graded doses of CCK-8 in conscious dogs with chronic gastric and duodenal fistulas. The lower dose of somatostatin-14 (S-14), which produced S-14 plasma levels lower than measured after a meal, did not change basal or stimulated pancreatic secretion. The upper dose of S-14, which produced plasma S-14 concentrations slightly above the postprandial range, caused inhibition of pancreatic fluid and protein secretion to low doses of CCK-8 (p less than 0.05). The inhibition was surmountable with higher doses of CCK-8. We interpret these data as indicating that circulating S-14 is not an important hormonal regulator of exocrine pancreatic secretion.

Animals↗
PubMed1986

Inhibition of pentagastrin-stimulated acid secretion after subcutaneous administration of a new somatostatin analogue.

Somatostatin, a peptide present in hypothalamus, gastric mucosa, and pancreas suppresses several gastrointestinal functions. Its short half life has prevented clinical use. We have therefore evaluated the effect of subcutaneous administration of a new synthetic somatostatin analogue, in comparison with a placebo, on pentagastrin stimulated acid secretion in six healthy volunteers. On different days, acid secretion was measured continuously, after a basal 30 minutes, for six hours during 3 micrograms/kg/h of intravenous pentagastrin. Acid secretion was measured with a marker technique (0.1% phenol red) to correct for duodenal volume loss. Blood was drawn in regular intervals to measure plasma somatostatin concentrations by radio immunoassay. One hour after starting the pentagastrin infusion, a single subcutaneous injection of either 100 micrograms somatostatin analogue, or placebo (isotonic saline) was given. In a follow up study, somatostatin was given subcutaneously in a dose of 200 micrograms. No difference in efficacy was observed between the two doses. A single subcutaneous injection of the somatostatin analogue significantly suppressed acid secretion for five hours (p less than 0.01). Maximal inhibition was approximately 75%. Mean elimination half life of the analogue was approximately 80 minutes. We suggest that the new somatostatin analogue might be useful for clinical use.

Adult↗
PubMed1986

Effect of exocrine pancreatic secretagogues on circulating somatostatin in dogs.

Several secretagogues of exocrine pancreatic secretion have been proposed to act as regulators of pancreatic D-cell function. To characterize this relationship, we measured incremental responses of protein, bicarbonate, and circulating somatostatin to graded doses of intravenous cholecystokinin (CCK-33), CCK-8, caerulein, bombesin, secretin, and intraduodenally perfused HCl, sodium oleate, and L-phenylalanine in conscious dogs with gastric and pancreatic fistulas and compared them with postprandial values (to a beef meal). Bombesin produced dose-related increases in somatostatin secretion (maximal, 46% of meal response), but caerulein, CCK-33, and CCK-8 released only small amounts of somatostatin at doses equivalent for pancreatic protein secretion. Secretin did not stimulate somatostatin release at any dose studied, whereas intraduodenal HCl at a load submaximal for pancreatic bicarbonate secretion increased somatostatin levels slightly (maximal, 16% of meal response). L-Phenylalanine and sodium oleate markedly increased protein secretion, but only oleate clearly stimulated somatostatin release (maximal, 11% of meal response). Our results suggest a greater quantitative importance of the intestinal phase for exocrine pancreatic stimulation than for somatostatin release.

Animals↗
PubMed1986

The effect of adding albumin to solutions of somatostatin (SST-14) on inhibiting pentagastrin-stimulated acid secretion in man.

The aim of this study was to identify the somatostatin (SST-14) dose dissolved in 0.1% human albumin solution equivalent to the commonly used therapeutic dose (3.5 micrograms kg-1 h-1) dissolved in saline in inhibiting pentagastrin-stimulated gastric acid secretion in healthy volunteers. Gastric acid secretion was stimulated for 3.5 h by intravenous pentagastrin (3 micrograms kg-1 h-1). 0.875 or 1.75 micrograms kg-1 h-1 SST-14 dissolved in 0.1% albumin was significantly (p less than 0.05) less effective in inhibiting stimulated gastric acid secretion than the standard therapeutic dose. There was no difference achieved in the degree of inhibition with albumin added or not to the 3.5 micrograms kg-1 h-1 dose of SST-14. However, an intermediate dose (2.625 micrograms kg-1 h-1) of SST-14, whether dissolved in albumin or saline alone, was as effective as the standard therapeutic SST-14 dose. We conclude that at these high does the absorption of a small quantity of SST-14 to glass and plastic surfaces of the infusion sets has no influence on the therapeutic effect.

Adult↗