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Biomedical subjects

C Beglinger

Publications and source records attributed to C Beglinger.

At least 217 records · Page 12Linked to original sources
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↗
PubMed1986

What is the maximal effective dose of caerulein in stimulating pancreatic secretion in man?

The pancreatic exocrine secretory response to increasing doses of exogenous caerulein with and without a background infusion of secretin was studied in 5 healthy volunteers. Caerulein over a full range of doses (2.3-37 pmol/kg/h) produced increasing enzyme secretion up to 18.5 pmol/kg/h, whereas 37 pmol/kg/h was clearly supramaximal and caused submaximal enzyme release. We conclude that maximal pancreatic enzyme secretion is achieved with lower caerulein doses than generally used in pancreatic function tests.

Adult↗
PubMed1986

Human pharmacological effects of SMS 201-995 on gastric secretion.

The inhibition of pentagastrin-stimulated-(3 micrograms kg-1 h-1) gastric acid secretion by various doses of intravenous and subcutaneous SMS 201-995, a somatostatin analogue, was investigated in healthy volunteers by means of gastric aspiration, using phenol red as a volume marker. The intravenous doses were compared with the standard dose of somatostatin-14, 3.5 micrograms kg-1 h-1. Similarly, SMS 201-995-induced inhibition of gastric acid secretion was compared with that of exocrine pancreatic secretion assessed by gastroduodenal aspiration. The results can be summarized as follows: SMS 201-995 is a potent inhibitor of gastric acid secretion, exerting near maximal inhibition at a dose of greater than or equal to 0.56 micrograms kg-1 h-1. Near maximal inhibition equals that achieved with SST-14 (3.5 micrograms kg-1 h-1). Pancreatic enzyme secretion appears to be strongly inhibited by lower doses of SMS 201-995 than gastric secretion. Single subcutaneous injections of SMS 201-995 produce an inhibition of gastric acid secretion lasting for many hours. Near maximal inhibition was obtained with a dose of 100 micrograms.

Adult↗
PubMed1985

[Interaction of the endo- and exocrine pancreas].

The pancreas has both exocrine and endocrine components. The exocrine component of the pancreas manufactures, stores, and packages digestive enzymes for digestion of food, whereas the endocrine secretes hormones that regulate the metabolism and utilization of the absorbed nutrient components. Both components are closely related, not only anatomically but also functionally. The available evidence to support the concept of a close interrelationship of endocrine and exocrine pancreatic function is summarized. It is shown that the endocrine part exerts a profound effect upon the digestive activities of the organ, and that impairment of endocrine function, such as diabetes, severely affects the exocrine component of the gland. Furthermore, dysfunction of the exocrine gland, as in chronic pancreatitis, progressively disturbs the function of the islet cell hormones. The interactions are governed by a complicated control system, the details of which are not yet clarified. As in any partnership, dysfunction of one partner severely affects the other and vice versa.

Animals↗
PubMed1985

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.

Adult↗
PubMed1984

Exocrine pancreatic secretion in response to a new CCK-analog, CCK33 and caerulein in dogs.

We studied the relative molar potencies of a newly synthetized cholecystokinin nonapeptide [Thr28,Nle31]CCK[25-33], natural porcine CCK33 and synthetic caerulein in conscious dogs with chronic gastric and pancreatic fistulas. Peptides were dissolved in albumin-containing solutions to prevent loss from solution. The three peptides were found to be equipotent on a molar basis in stimulating exocrine pancreatic secretion. As [Thr28,Nle31]CCK9 is a peptide less susceptible to oxidation than other forms of CCK, it is an interesting analog with many uses for medical and biological research.

Animals↗