[Gastrointestinal hormones as tools of clinical diagnosis].
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The principle and types of saturation analysis are discussed on the basis of data in the literature. This is followed by summarizing the main steps of radioimmunoassay (RIA) of gastrointestinal hormones. The normal fasting blood levels of these hormones are also given. RIA measurement of the individual hormones is discussed critically, and attention is called to the theoretical importance of immune cross-reactions. The RIA model developed by the author for measuring the C-terminal pentapeptide of gastrin is demonstrated.
Obesity has been described as the greatest current threat to human health. In order to design drugs to target obesity, it is essential to understand its physiology and pathophysiology. Several peptides synthesised in the gastrointestinal tract which affect food intake have been identified including ghrelin, cholecystokinin (CCK), glucagon-like peptide-1 (7-36) amide (GLP-1), oxyntomodulin, peptide YY (PYY) and pancreatic polypeptide (PP). These peptides represent potential targets for the design of anti-obesity drugs. In this article we review recent advances in our understanding of food intake by these gastrointestinal hormones.
There is no general agreement as regards the effect of Helicobacter pylori infection on gastric emptying in patients with functional dyspepsia. Food releases several gastrointestinal hormones, and some of these are known to contribute to the regulation of gastric emptying. The aim of this study was to investigate the influence of H. pylori on gastric emptying in dyspeptic and healthy subjects and to verify whether different hormone secretion patterns are affected by the presence of the bacterium. Twenty-seven patients affected by functional dyspepsia and 30 asymptomatic healthy subjects entered the study. H. pylori presence was assessed in controls by IgG antibodies to H. pylori and [13C] urea breath test, and that in patients by Warthin-Starry stain on gastric biopsies. After ingesting a standard solid-liquid meal, an ultrasound examination of gastric emptying was performed. Plasma concentrations of gastrin, cholecystokinin, and pancreatic polypeptide were measured in the fasting and postprandial period for 4 hours. The incidence of H. pylori infection was not higher in functional dyspepsia patients than in controls. As regards gastric emptying, no difference was detected between patients and controls with and without H. pylori infection. On the contrary, the presence of H. pylori infection determined alterations in gastrin levels, which were higher in controls than in patients. Basal CCK levels were higher in the H. pylori-negative patients than H. pylori-positive patients and controls. In conclusion, H. pylori infection seems not to cause alterations in gastric emptying, but rather alterations in gastrin levels. In contrast, the altered levels of CCK account for its involvement in the pathophysiology of H. pylori-negative dyspepsia.
A rapid reversed-phase high-performance liquid chromatography method was developed for the isolation of small quantities of biologically active gastrointestinal hormones, using a Varian MCH-10 C18 column. Biologically active secretin was isolated from contamination with other hormones, including cholecystokinin, gastrin, motilin, and vasoactive intestinal polypeptide, from samples of the acid perfusate of canine duodenum and from the crude acetic acid extract of canine antral mucosa containing less than 100 picomoles of secretin. The method also appeared to be suitable for the isolation of cholecystokinin octapeptide and motilin.
The injection of trimebutine induces in the dog an increase of plasma motilin during the fasting period as well as after a meal. We studied the effect of trimebutine on several gastrointestinal hormones released into the circulation by the ingestion of a meal. The intravenous administration of trimebutine (10 mg/kg/h) in 4 dogs abolished the postprandial increase in plasma gastrin, pancreatic polypeptide, insulin, glucagon and GIP. Trimebutine could therefore, by its effects on various regulatory peptides, influence several digestive functions. Its mode of action could probably involves complex mechanisms, including paradoxical effects. The possibility that motilin is a mediator of the trimebutine effect on small bowel smooth muscle is discussed.
In monogastric animals, suckling influences the secretion of gastrointestinal hormones during lactation. The aim of the present study was to investigate whether similar effects are induced by milking in cows. Experiments were performed on four cows in midlactation. Blood samples were drawn from a chronic jugular vein catheter and gastrin, and somatostatin were determined by radioimmunoassay. Milking and feeding increased plasma gastrin. Somatostatin increased at morning milking and at feeding, but it decreased at evening milking. Atropine injected subcutaneously 30 min before milking increased resting concentrations of gastrin but decreased resting concentrations of somatostatin. Feeding-induced release of gastrin remained but the milking-induced release disappeared. The milking- and feeding-induced effect on somatostatin became more marked. We suggest that milking influences gastrin and somatostatin via activation of the vagal nerves. The gastrin release caused by milking may be mediated via a cholinergic mechanism, whereas the atropine resistant effect on gastrin caused by feeding and on somatostatin caused by both milking and feeding suggest that a noncholinergic, perhaps peptidergic, transmitter may be involved.
Tocamphyl is a synthetic choleretic that is derived from a root extract of Curcuma longa, L. We investigated the effect of tocamphyl on pancreatic exocrine secretion and bile flow, and on the release of some gastrointestinal hormones, by administering it intraduodenally using anesthetized rats. Tocamphyl stimulated pancreatic exocrine secretion in terms of volume and amylase output in a dose-related manner. Neither a CCK-receptor antagonist, CR1505 (loxiglumide), nor atropine sulfate infused intravenously suppressed the stimulatory effects of tocamphyl on pancreatic exocrine secretion and bile flow. The stimulatory effect on bile flow was stronger than that on pancreatic exocrine secretion. Plasma secretin levels were augmented with the increasing doses of tocamphyl, but CCK levels were not. These results indicate that intraduodenally administered tocamphyl stimulates pancreatic exocrine secretion and bile flow, and suggest that the stimulatory action is, at least in part, mediated by secretin, but not by either CCK or the cholinergic pathway.
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To investigate the mechanisms by which intestinal carbohydrate affects eating behavior, seven fasted, healthy male volunteers received intraduodenal infusions of glucose or saline over a 90-min period while blood glucose levels were matched by use of intravenous glucose and saline infusions. A second study examined the effect of intraduodenal glucose on eating behavior when the gastrointestinal hormone response was inhibited by intravenous octreotide. Intravenous glucose infusion did not affect hunger or satiety. In contrast, intraduodenal infusion of glucose suppressed hunger, increased fullness and satiety ratings, reduced energy intake, and resulted in higher plasma insulin responses compared with the intravenous glucose infusion. Octreotide abolished the plasma insulin response to intraduodenal glucose and reversed the changes in ratings and eating behavior. This study has shown that the effects of intestinal glucose on appetite are not mediated via an increase in blood glucose but are likely to reflect small intestinal stimulation of release of either insulin or intestinal incretins.
The smooth muscle sphincter enveloping the terminal portion of the common bile duct in the opossum exhibits spontaneous electrical activity and simultaneous rhythmic contractions. The aim of our study was to define the influence of four gastrointestinal hormones on biliary sphincter electrical and mechanical activity. An array of five monopolar extracellular electrodes was placed along the opossum choledochal sphincteric smooth muscle and contiguous duodenum. A catheter in continuity with a pressure transducer, drop counter, and saline reservoir was placed in the common duct for simultaneous measurement of ductal pressure and flow. The cystic and distal common hepatic ducts were then ligated to isolate the common bile duct from the gallbladder and liver. In each opossum, biliary sphincteric and duodenal myoelectric activity, common bile duct and gallbladder pressure, and common duct flow were recorded simultaneously before and after the intravenous administration of five different doses of an enteric hormone. Ten animals were given 0.1-10.0 international dog units per kilogram body wt of cholecystokinin, 10 received 0.01-1.00 microgram/kg body wt of cholecystokinin-octapeptide, 10 were given 0.1-10.0 micrograms/kg body wt of secretin, and 5 were given 0.1-10.0 micrograms/kg body wt of pentagastrin. Cholecystokinin, cholecystokinin-octapeptide, and pentagastrin all effected a significant increase in sphincter electrical spike activity and common duct pressure with a decrease in common duct flow. This contractile response was consistent at a wide range of hormonal levels. Secretin had little effect on biliary pressure, flow, and myoelectric activity. The data lend support to the concept that cholecystokinin and gastrin contract the biliary sphincter, metering bile flow at the time of gallbladder emptying in the opossum.
It is not known if the increased plasma concentration of noradrenaline in patients with chronic duodenal ulcer disease is a pathogenetic factor or not. The aim of the present study was to investigate if physiologic changes of noradrenaline would evoke any alterations in gastric acid secretion or in the plasma concentration of some gastrointestinal hormones (gastrin, secretin, PP, PYY, and GIP) known to affect gastric physiology. The results show that basal plasma noradrenaline concentration was 1.8 nM and after infusion with noradrenaline at 0.04 or 0.2 nmol/kg/min plasma levels of 2.5 and 4.4 nM were obtained. No appreciable changes could be found in basal or pentagastrin stimulated acid secretion or in any of the gastrointestinal peptides studied. If the elevated plasma noradrenaline concentration observed in duodenal ulcer patients is a pathogenetic factor; it is probable that it interferes with other variables such as blood flow, bicarbonate secretion, or prostaglandin synthesis.
The use of an elemental diet in the early postoperative or posttraumatic period is more and more common. Discussions about pancreatic stimulation during enteral infusion of an elemental diet are still contradictory. The aim of this study was to give some possible explanations on pancreatic and biliary secretion and the response of gastrointestinal hormones to an elemental diet infused into the jejunum in the early postoperative period. We therefore developed an experimental model in pigs. As our results show, there is an increased output of amylase in jejunal secretion when enteral feeding is started. Further a reduced biliary secretion which is possibly due to the reduced content of long-chained triglycerides in the used diet. The insulin and somatostatin levels remained within normal ranges during the whole period of investigations. We thought this to be an effect of the continuous pump controlled infusion of the diet. The slight hyperglucagonemia is explained by the surgical trauma. These findings support the usefulness of an elemental diet in the early postoperative period. Whether the benefits of an early enteral feeding can be used in acute pancreatitis needs further investigations.
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