Irrigation et sécrétion gastriques après ligature ou fistule pyloriques chez le rat,sous l'influence d'huile d'olive intra-duodénale

Summary Pylorus ligature hides the inhibitory effects of endogenous cholecystokinine-pancreozyme (CCK-PZ) on gastric mucosal secretion and irrigation, whereas the juice collected through transduodenal pyloric fistula makes this phenomenon obvious. It appears that the pyloric fistula encourages inhibition of gastrinic secretion, so that the CCK-PZ can achieve its effects.     

Possible cellular localization of cholecystokinin-pancreozymin

Zusammenfassung Nach intraduodenaler Stimulation der Cholecystokinin-Pancreozymin Sekretion (CCK-PZ) beim Hund durchl-Phenylalanin finden sich Anhaltspunkte für die Ausschleusung von Sekretgranula bei 2 Typen von endokrinen Zellen. Es handelt sich einerseits um enterochromaffine Zellen (EC), die 5-Hydroxytryptamin produzieren und deren Verteilung im Gastrointestinaltrakt nicht dem CCK-PZ entspricht, andererseits um D-Zellen, deren Hormonalprodukt noch nicht identifiziert ist. Es wird angenommen, dass CCK-PZ von den D-Zellen des Gastrointestinaltraktes produziert wird.     

Inhibitory action of cholecystokinin-pancreozymin on gastric pepsin secretion

Zusammenfassung Der Einfluss von Cholecystokinin-Pankrcozymin auf die Sekretion von Pepsin wurde in Hunden mit Heidenhain-Tasche untersucht. Während submaximaler Pepsinstimulation mit Mecholyl verminderte i.v. Injektion von Cholecystokinin-Pankreozymin die Pepsin-Sekretion im Magen signifikant. Es wird vermutet, dass CCK-PZ Enterogastrone sein könnte.     

Relationship of phosphatidylcholine to hydrophobic surfactant on rat intestinal chylomicron secretion

Hydrophobic surfactants such as Poloxalene inhibit triglyceride secretion into lymph by enterocytes. The inhibitory effect of these agents on triglyceride secretion is reversed when lipid presented for absorption is exclusively in the form of phosphatidylcholine (PC) and not triglyceride. The present investigation performed in conscious mesenteric lymph fistula rats was designed to determine whether various mixtures of triglyceride and PC given intraduodenally with Poloxalene would also reverse the inhibitory effect of Poloxalene on triglyceride secretion into lymph. A 50–50 mixture of triolein (TO) and PC resulted in normal triglyceride secretion into lymph. However, when the mixture of lipids was 75-25, TO to PC, results for triglyceride recovery in lymph were considerably reduced. The transport rate for triglyceride into lymph was not as depressed, however, as observed for Poloxalene treated rats given lipid for absorption basically in the triglyceride form. Substitution of phosphatidylethanolamine for PC had no beneficial effect on triglyceride secretion in Poloxalene treated rats. It is concluded that PC can reverse the inhibitory effect of Poloxalene on triglyceride secretion into lymph even when considerable amounts of triglyceride along with PC are presented for absorption.     

Immunological blocking of exogenous and endogenous secretin in the dog.

In mongrel dogs with chronic gastric and duodenal fistula the biological activity of secretin on exocrine pancreatic secretion could be blocked by preincubating the secretin injected with rabbit antisecretin antibody. In addition, the activity of endogenous secretin released by acid was markedly reduced by application of antibody. Since no such effect was observed after testmeal stimulation, secretin is most probably not released in a significant amount by the liquid meal used in this experiment.     

The islet-acinar axis of the pancreas: Is there a role for glucagon or a glucagon-like peptide?

Intravenous glucagon inhibits exocrine pancreatic secretion in vivo, but exogenous glucagon does not affect exocrine secretion in vitro. Recent work, however, suggested that endogenous glucagon may be involved in the regulation of exocrine secretion even in vitro. We therefore investigated the effects of exogenous and endogenous glucagon on exocrine secretion by the isolated perfused rat pancreas in the presence of 1.8 mM glucose. Exogenous glucagon did not affect CCK-stimulated amylase output. 20 mM arginine stimulated glucagon release, but did not affect basal enzyme secretion. CCK-stimulated amylase output, however, was significantly inhibited in the presence of arginine. This inhibitory effect of arginine on exocrine pancreatic secretion could be blocked by glucagon antibodies, but not by nonspecific gammaglobulins. Thus exogenous glucagon failed to affect exocrine pancreatic secretion in vitro, but endogenously released glucagon or a glucagon-like peptide inhibited amylase release in the isolated perfused pancreas. We conclude that glucagon or a glucagon-like peptide may be a mediator in the islet-acinar axis.     

Role of protein kinase C and Ca2+ in glucose-induced sensitization/desensitization of insulin secretion.

The role of protein kinase C and Ca2+ in glucose-induced sensitization/desensitization of insulin secretion was studied. A 22-24 h exposure of mouse pancreatic islets to glucose (16.7 mmol/l) in TCM 199 culture medium, with 0.26 mmol/l or 1.26 mmol/l Ca2+, reduced total islet protein kinase C activity to approx. 85% and 60% of control values, respectively. At 0.26 mmol/l Ca2+ in TCM 199 medium, exposure to glucose (16.7 mmol/l) led to a potentiation of both phase 1 and phase 2 of glucose-induced insulin secretion, and caused a shift in the dose-response curve with 10 mmol/l and 16.7 mmol/l glucose exhibiting equipotent effects in stimulation of insulin secretion. In glucose-sensitized islets, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (0.16 mumol/l) did not further potentiate induction of secretion by 10 mmol/l or 16.7 mmol/l glucose. At 3.3 mmol/l glucose, however, phorbol ester-induced secretion was augmented, and was characterized by a faster onset of secretion in glucose-sensitized islets relative to control islets. In contrast, a partial reduction in arachidonic acid (100 mumol/l)-induced insulin release was observed in glucose-sensitized islets in the absence of extracellular Ca2+. Increasing the Ca2+ concentration to 1.26 mmol/l in TCM 199 during the 22-24 h exposure to glucose (16.7 mmol/l) led to inhibition of phase 1 and abolition of phase 2 of glucose (10 mmol/l, 16.7 mmol/l)-induced insulin secretion. In addition, this treatment abolished phorbol ester-induced and arachidonic acid-induced insulin secretion at 3.3 mmol/l glucose. Altogether, these data suggest that sensitization of insulin secretion is caused by a preferential down-regulation of the inhibitory effects of protein kinase C, leading to an increased first phase, and an increased coupling of glucose to the stimulatory effects of protein kinase C during the second phase of glucose-induced insulin secretion. Desensitization of insulin secretion appears to be a consequence of sustained Ca2+ influx, inducing extensive down-regulation of protein kinase C and also causing deleterious effects on islet cell function in protein kinase C-deprived islets.     

Role of protein kinase C and Ca2+ in glucose-induced sensitization/desensitization of insulin secretion

The role of protein kinase C and Ca²⁺ in glucose-induced sensitization/desensitization of insulin secretion was studied. A 22–24h exposure of mouse pancreatic islets to glucose (16.7 mmol/l) in TCM 199 culture medium, with 0.26 mmol/l or 1.26 mmol/l Ca²⁺, reduced total islet protein kinase C activity to approx. 85% and 60% of control values, respectively. At 0.26 mmol/l Ca²⁺ in TCM 199 medium, exposure to glucose (16.7 mmol/l) led to a potentiation of both phase 1 and phase 2 of glucose-induced insulin secretion, and caused a shift in the dose-response curve with 10 mmol/l and 16.7 mmol/l glucose exhibiting equipotent effects in stimulation of insulin secretion. In glucose-sensitized islets, the phorbol ester 12-O-tetradecanoylphorbol 13-acetate (0.16 μmol/l) did not further potentiate induction of secretion by 10 mmol/l or 16.7 mmol/l glucose. At 3.3 mmol/l glucose, however, phorbol ester-induced secretion was augmented, and was characterized by a faster onset of secretion in glucose-sensitized islets relative to control islets. In contrast, a partial reduction in arachidonic acid (100 μmol/l)-induced insulin release was observed in glucose-sensitized islets in the absence of extracellular Ca²⁺. Increasing the Ca²⁺ concentration to 1.26 mmol/l in TCM 199 during the 22–24h exposure to glucose (16.8 mmol/l) led to inhibition of phase 1 and abolition of phase 2 of glucose (10 mmol/l, 16.7 mmol/l)-induced insulin secretion. In addition, this treatment abolished phorbol ester-induced and arachidonic acid-induced insulin secretion at 3.3 mmol/l glucose. Altogether, these data suggest that sensitization of insulin secretion is caused by a preferential down-regulation of the inhibitory effects of protein kinase C, leading to an increased first phase, and an increased coupling of glucose to the stimulatory effects of protein kinase C during the second phase of glucose-induced insulin secretion. Desensitization of insulin secretion appears to be a consequence of sustained Ca²⁺ influx, inducing extensive down-regulation of protein kinase C and also causing deleterious effects on islet cell function in protein kinase C-deprived islets.     

Inhibitory effect of ouabain on in vitro and in vivo gastric acid secretion in the frog and the rat

The in vitro and in vivo effects of ouabain on gastric acid secretion in the frog and the rat, the 2 species known to have different sensitivity to ouabain, were studied. It was found that ouabain was a potent inhibitor of histamine-stimulated acid secretion in the isolated frog gastric mucosa. Ouabain administered i.v. at dose levels far below the lethal range also produced a marked and significant reduction of histamine-stimulated gastric acid secretion in the anesthetized frogs and rats. It is considered that the inhibitory effect of ouabain on acid secretion could be partly related to its specific antagonizing action on the Na+ -K+ -ATPase in the gastric mucosa.     

Immunofluorescent demonstration of pancreatic polypeptide (PP) in pancreas and digestive tube of bony and cartilaginous fish]

When antisera specific against bovine PP (BPP) were used, immunoreactive parenchymal cells were observed in the endocrine pancreas and in the gastro-intestinal tract of the teleost bony fish Cottus scorpius, as well as in the pancreas of the elasmobranchian cartilaginous fish Squalus acanthias. Of the two principal islets of Cottus, PP-cells were located selectively to that in the pyloric region.     

Inhibitory effect of ouabain on in vitro and in vivo gastric acid secretion in the frog and the rat

Summary The in vitro and in vivo effects of ouabain on gastric acid secretion in the frog and the rat, the 2 species known to have different sensitivity to ouabain, were studied. It was found that ouabain was a potent inhibitor of histamine-stimulated acid secretion in the isolated frog gastric mucosa. Ouabain administered i.v. at dose levels far below the lethal range also produced a marked and significant reduction of histamine-stimulated gastric acid secretion in the anesthetized frogs and rats. It is considered that the inhibitory effect of ouabain on acid secretion could be partly related to ist specific antagonizing action on the Na⁺-K⁺-ATPase in the gastric mucosa.     

Absorption of double labeled (glycerol 3H-linoleic acid 14C) native bile by phosphatidylcholines]

Double-labeled bile ([U. 3H glycerol] [1. 14C linoleic acid])--in which about 70% of labeling 14C and 80% of labeling 3H of total lipids were borne by phosphatidylcholines (PC), (isotopic ratio of these PC was equal to 1)--was introduced into the duodenum of test Rats, some of them with a bile fistula. As low amounts of the hydrolysis products of biliary PC were found in the intestinal lumen, a higher hydrolysis must occur further (brush border, enterocyte ?) because, in the mucosa, the highest labeling 14C was present as triglycerides and PC have an isotopic ratio 3H/14C higher than 1. As in the lumen the isotopic ratio 3H/14C of PC was higher than 1 and increased with the time elapsed, this finding suggests that mucosal PC were added to biliary PC (secretion or desquamation ?) unless these modifications were due to luminal micro-organisms. As test Rat bile was poorly labeled a very weak enterohepatic circulation of biliary diunsaturated PC may exist.     

Somatostatin immunoneutralization overcomes the inhibitory effects of quipazine and pargyline on growth hormone secretion in domestic fowl

The inhibitory effects of pargyline and quipazine on chicken growth hormone secretion were overcome by passive immunoneutralization of endogenous somatostatin (SRIF)-14 or SRIF-28(1-14)-like immunoreactivity. Administration of the specific antisera to control birds pretreated with 0.9% NaCl elevated the basal plasma GH concentrations. These results suggest that peptides with SRIF-14 or SRIF-28(1-14)-like immunoreactivity tonically inhibit GH secretion and are at least partially responsible for the inhibitory effects of pargyline and quipazine on GH release in immature domestic fowl.     

Factors influencing the intestinal phase of pancreatic exocrine secretion in the turkey

The present study was done to investigate the factors regulating the intestinal phase of exocrine pancreatic secretion in the turkey. The intestine of turkeys equipped with pancreatic fistulas was perfused with peptone solution, fat emulsion and hydrochloric acid (HCl), and pancreatic flow and protein output were measured. Neither peptone solution nor fat emulsion had any effects on pancreatic secretion. HCl enhanced the flow rate of pancreatic juice but not protein output. To clarify the neural mechanism of this phenomenon, the vagal postganglionic blocker atropine was continuously infused and pancreatic secretion in response to intestinal HCl was measured. Atropine completely suppressed both pancreatic flow and protein output. It is suggested that the avian intestinal phase of pancreatic secretion is mainly controlled by cholinergic action though HCl stimulation.     

Somatostatin immunoneutralization overcomes the inhibitory effects of quipazine and pargyline on growth hormone secretion in domestic fowl

Summary The inhibitory effects of pargyline and quipazine on chicken growth hormone secretion were overcome by passive immunoneutralization of endogenous somatostatin (SRIF)-14 or SRIF-28(1–14)-like immunoreactivity. Administration of the specific antisera to control birds pretreated with 0.9% NaCl elevated the basal plasma GH concentrations. These results suggest that peptides with SRIF-14 or SRIF-28(1–14)-like immunoreactivity tonically inhibit GH secretion and are at least partially responsible for the inhibitory effects of pargyline and quipazine on GH release in immature domestic fowl.     

Influence of an injection of chorionic hormone (HCG) on the accumulation of testicular fluid following ligature of the vas deferens in adult Wistar rats]

Using the weight gain of the testis after efferent duct ligation, we have measured the testis fluid secretion. A single injection of HCG to Rats before, at the time or after the ligation leads to three types of effects: no effect which can be explained by the metabolisation of the hormone: a positive and/or a negative one. If the stimulating action of HCG remains unexplained, it must be related with ether anaesthesia. It seems likely that the decrease of testicular fluid secretion may represent the fundamental action of HCG upon the exocrine function of the testis, but the mecanism by which this action occurs remains to be solved.     

Immunological blocking of exogenous and endogenous secretin in the dog

Summary In mongrel dogs with chronic gastric and duodenal fistula the biological activity of secretin on exocrine pancreatic secretion could be blocked by preincubating the secretin injected with rabbit antisecretin antibody. In addition, the activity of endogenous secretin released by acid was markedly reduced by application of antibody. Since no such effect was observed after testmeal stimulation, secretin is most probably not released in a significant amount by the liquid meal used in this experiment.This work was supported by grant No. 3.816-0.76 of the Swiss National Foundation for Scientific Research.We express our thanks to Miss G. van Hees, Mrs L. Jecker and Dr F. Meyer for their excellent technical assistance, Dr W. W. Rittmann for the surgical support, Dr G.A. Stalder for general advice, Dres R. Studer and D. Gillessen for providing secretin Roche, and Mrs C. Frei for secretarial work.     

Dysfunctional insulin secretion in type 2 diabetes: role of metabolic abnormalities

Insulin secretion is finely tuned to the requirements of tissues by tight coupling to prevailing blood glucose levels. The normal regulation of insulin secretion is coupled to glucose metabolism in the pancreatic B cell, a major but not exclusive signal for secretion being closure of K⁺ATP (adenosine triphosphate)-dependent channels in the cell membrane through an increase in cytosolic ATP/adenosine diphosphate. Insulin secretion in type 2 diabetes is abnormal in several respects due to genetic causes but also due to the metabolic environment of the pancreatic B cells. This environment may be particularly important for the deterioration of insulin secretion which occurs with increasing duration of diabetes. Factors in the environment with potential importance include overstimulation, a negative effect of hyperglycemia per se (‘glucotoxicity’) as well as adverse effects of elevated fatty acids (‘lipotoxicity’). Elucidating the mechanisms behind these factors as well as their clinical importance will pave the way for treatment which could preserve B-cell function in type 2 diabetic patients. Received 4 October 1999; received after revision 1 November 1999; accepted 3 December 1999     

Nerve-mediated action of forskolin on guinea pig ileal mucosa

The effects of forskolin on myenteric neuronal activity and mucosal function were examined in guinea pig ileum. Forskolin increased the excitability of myenteric neurons, and increased mucosal chloride secretion by stimulating enteric neurons as well as by acting directly on enterocytes.     

Action of histamine and vasoactive intestinal peptide (VIP) on cyclic AMP in gastric glands isolated from human fetal stomach

Histamine and VIP produce an elevation of cAMP production in gastric glands isolated from the human fetal stomach at 15 weeks gestation. These effects were attributed to the activation of 2 distinct receptor-cAMP systems, one being sensitive to histamine in parietal cells, and the other being sensitive to VIP in muco-peptic cell populations. The results suggest that histamine and VIP may play a role in inducing gastric secretion during fetal life in man.