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Hormonal control of gastrointestinal motility.

The motor responses of the gastrointestinal tract to a meal are tuned to provide the optimal conditions for digestion and absorption of food. Hormones released from the mucosa of the intestinal tract play an important role in regulating and integrating the various motor events which occur. Complex feedbacks, both nervous and humoral, control the release of intestinal hormones and also modify their actions. Preliminary studies suggest that abnormalities in the secretion or action of various gastrointestinal hormones may play an important role in the production of motor disorders of the gastrointestinal tract.

Cholecystokinin↗

Dietary fibre enrichment, blood pressure, lipoprotein profile and gut hormones in NIDDM patients.

The influence of a beet-fibre enriched diet (mean 40 g FibrexR, 27 g dietary fibre per day) on blood pressure, plasma lipoproteins and glycaemic control was studied in 12 non-insulin-dependent diabetic (NIDD) patients. The effect on gastrointestinal hormones was also investigated. Beet-fibre and control diets were given in randomized order for 8 weeks each. During the beet-fibre diet the systolic blood pressure decreased (P less than 0.05) and the HDL-cholesterol levels increased (P less than 0.05) compared to values before the study. There was a tendency for systolic blood pressure to be lower also in the control period, but this was not statistically significant. After both diet periods the total plasma cholesterol and triglyceride levels decreased, as well as the LDL/HDL ratio. Blood glucose levels--fasting or postprandial--and glycosylated haemoglobin were not affected during the two different diet periods. In obese NIDD patients, however, the postprandial insulin levels were lower after the beet-fibre diet compared to the control diet. This subgroup also showed lower fasting values of pancreatic polypeptide and motilin were recorded for the obese patients after the fibre-rich period compared to before the study. Further, increases in postprandial motilin levels, 60-180 min, were found after the fibre-rich period. Investigations with reference to an entero-hormonal mechanism by measuring neurotensin and peptide YY did not show any variations between the diet periods.

Adult↗

Differential activities of two distinct endothelin family peptides on ileum and coronary artery.

A synthesized mouse vasoactive intestinal contractor peptide, which belongs to a novel member of the endothelin family, induced a prolonged contraction in mouse ileum as well as porcine coronary artery in vitro. Studies comparing the effects of vasoactive intestinal contractor and endothelin on different tissues revealed that the maximum ileum contraction of vasoactive intestinal contractor was much higher than that of endothelin in both guinea pig and mouse systems, but that the vasoconstriction activity of vasoactive intestinal contractor was weaker than that of endothelin in porcine artery. These results show that vasoactive intestinal contractor might be a novel gastrointestinal hormone.

Animals↗

[The adaptational-compensatory reactions of the digestive system during the development of pancreatic atrophy].

Adaptive-compensatory processes have been revealed in the digestive system in pancreatic atrophy. These processes promote: a) the compensation of the pancreatic enzymatic insufficiency and of the cavitary digestion decrease by the alpha-amylase adsorbed at the small intestinal epithelium, b) the increasing of the intestinal pH, c) the keeping up of the postprandial levels of gastrointestinal hormones.

Adaptation, Physiological↗

[Pathomorphologic studies of the endocrine cells in the gastrointestinal mucosa. Physiology, cytochemistry and ultrastructure (author's transl].

With combined immunofluorescent, cytochemical and electron microscopic investigations the enterochromaffin cell system has been differentiated into 5 distinct endocrine cell types in the human stomach and into 8 cell types in the intestine. These endocrine cells are probably of neuroectodermal origin and belong to the APUD (amine precursor uptake and decarboxylation)-system. Maximal gastrointestinal hormone concentrations as determined by tissue extracts correlate fairly well to the location of each endocrine cell type in various segments of the gastrointestinal tract. In certain gastroenteropathies the pathophysiological disturbances can be explained by pathomorphological alterations of the disseminated endocrine cells. 1. The gastrin-producing G-cell is the predominating endocrine cell in the gastric antrum. Besides immunocytochemistry the G-cell can be demonstrated with argyrophilic reaction (Grimelius, 1968), masked metachromasia and leadhematoxylin. The ultrastructural features are variable, depending on functional activity. The secretory granules are usually only slightly osmiophilic, measuring 200 till 250 nm in diameter. By some working groups a positive immunofluorescence with gastrin-antisera has been demonstrated in A1- or D-cells of the pancreatic islets. However, numerous negative results have been reported, too. Considering physiological conditions, a gastrin-secretion of the human pancreatic islets has not been secured without doubt. 2. The EC-cell produces serotonin and in the intestine motilin, too. Besides the formaldehyde-induced fluorescence, these cells can be demonstrated with diazonium and argentaffin reactions, less specific with argyrophilic methods. Ultrastructurally the EC-granules are easily differeniated from the other endocrine cells by their pronounced osmiophilia and pleomorphism. In experimental conditions the EC-cells demonstrate species- and site-specific alterations. With reserpine no ultrastructural changes were demonstrable in EC-cells of the rat. However, marked ultrastructural alterations with an increase of the hormone-producing organelle system were noticed after administration of parachlorophenylalanine (PCPA) which interferes with serotonine synthesis; 5. The gastric D-cells are characterized by large secretory granules similar to pancreatic D-cells. They secrete the HCl-inhibitory peptide somatostatin. 4. The D1-cell is a cell type with unknown function. The cytoplasm contains small granules with variable electron density. According to most authors, they represent a distinct cell type and not just a variant of the G-cells. It may be very difficult, however, to separate certain forms of D1-cells from functionally altered G-cells. 5. The A-cell can be found in the gastric mucosa of certain animal species, where it has been demonstrated by immunocytochemistry with antisera to gut-glucagon. This cell type does not occur in the human gastric mucosa. 6...

Adenoma, Islet Cell↗

An experimental study on cell dynamic alteration in digestive organs following total parenteral nutrition in dogs.

To investigate the effects of total parenteral nutrition (TPN) on the alimentary tract, liver and pancreas, dogs were kept under TPN for 3 weeks, and changes in the cell dynamics of those organs and gastrointestinal hormones were evaluated. DNA synthesis activity in the mucosa of the stomach, jejunum and ileum decreased after TPN, and these changes recovered after oral refeeding. However, in the nonmucosal structures of the gastrointestinal wall, liver and pancreas, no corresponding changes were observed. Serum gastrin concentration was lowered after TPN, and it recovered after oral refeeding. A positive correlation was observed between serum gastrin level and DNA synthesis activity in the mucosa of the stomach, jejunum and ileum at all periods. However, enteroglucagon and pancreatic glucagon in the blood did not show any changes after TPN. In conclusion, TPN-induced changes in cell dynamics in the mucosa of the alimentary tract are reversible after resumption of oral feeding, and the serum gastrin release may be a regulating factor in these changes.

Animals↗

The scientific growth of gastroenterology during the 20th century. The 1994 G. Brohee Lecture.

Energized by the growth of the basic sciences during the latter half of the 20th century, gastroenterology advanced from a modest clinical activity to an increasingly scientific discipline. The decisive change followed World War II, when the Office of Scientific Research and Development transferred university and industry wartime research contracts to the National Institutes of Health (NIH), followed by establishment of the National Science Foundation and the General Medicine Study Section (NIH). Other factors contributing to the progress of gastroenterology included: (1) the increasing body of scientific knowledge; (2) innovative technological advances; (3) philanthropic, pharmaceutical, and governmental (NIH) support of research; (4) emphasis on controlled clinical and laboratory studies; and (5) the enlarging global scientific communication network. Selected highlights on the evolving knowledge of gastrointestinal hormones and the discovery of cholecystography illustrate some of the pathways of gastroenterology's 20th century advance.

Cholecystography↗

Manometric and hormonal changes after distal partial gastrectomy.

BACKGROUND: Alkaline oesophagitis attributable to duodenal mechanisms may induce oesophageal carcinogenesis in a rat reflux model. AIM: To investigate the mechanism of the regurgitation after distal partial gastrectomy. METHODS: Oesophageal manometry was used in 16 patients before and after distal partial gastrectomy with reconstruction by Bilroth methods. Serum concentrations of four gastrointestinal hormones were measured by radioimmunoassay in 10 gastrectomy patients and nine healthy volunteers before and after a standardized meal. RESULTS: The lower oesophageal sphincter pressure was reduced to 83% after surgery. The amplitude and duration of the peristaltic waves tended to be increased, and the velocity tended to be less after surgery (amplitude 120%, duration 114%, velocity 88%). Interrupted waves appeared more frequently after surgery. The manometric changes in gastrectomized patients are considered to be disadvantageous relative to regurgitation. After surgery, gastrin and pancreatic polypeptide were completely abolished postprandially, whereas cholecystokinin and neurotensin were significantly increased. CONCLUSION: The hormonal changes should have a suppressive effect on the lower oesophageal sphincter. Both the manometric and the hormonal changes may exacerbate reflux oesophagitis after distal partial gastrectomy.

Aged↗

Effect of jejunal infusion of different caloric loads on pancreatic enzyme secretion and gastro-intestinal hormone response in man.

It has recently been demonstrated that the infusion of a high caloric load (3.3 kcal min-1 = 14.0 kJ min-1) into human upper jejunum inhibited pancreatic enzyme and bile salt secretion. The aim of the present study was to investigate whether this phenomenon was mediated by gastrointestinal hormones which interfere with pancreatic secretion. In six healthy volunteers, jejunal infusion of 1.3 kcal min-1 (5.5 kJ min-1) did not modify secretion of lipase and chymotrypsin to any significant extent compared with saline infusion, but the rate of 3.3 kcal min-1 (14.0 kJ min-1) resulted in an inhibition. Somatostatin and pancreatic polypeptide, which are known to inhibit exocrine pancreatic secretion, remained unchanged during jejunal nutrient infusion. The inhibition of pancreatic enzyme secretion was observed in temporal relationship with an increase of the stimulators of pancreatic exocrine secretion such as secretin, neurotensin, and CCK. The existence of an hitherto undefined inhibitor and a feedback mechanism is postulated.

Adult↗

Acceleration of peritoneal mass transport by drugs and hormones.

The major restrictions to the transport of solute and solvent across the peritoneum are the limited peritoneal blood flow, area and permeability. Recent investigations have demonstrated that several vasoactive drugs influence transport parameters. Isoproterenol, nitroprusside, dipyridamole and dopamine exemplify drugs that dilate the splanchnic vasculature, thereby augmenting transport, whereas vasoconstriction induced by l-norepinephrine decreases clearances. The tissue prostaglandins affect peritoneal mass transport in accord with their known vasoactive effects, suggesting a role in modulating peritoneal blood flow. The gastrointestinal hormones vasodilate the splanchnic circulation. Exposure of the endothelial surface to glucagon markedly increases peritoneal mass transport, while secretin increases the ultrafiltration rate significantly. These preliminary studies suggest the possible future clinical use of drugs and hormones to augment the efficiency of peritoneal dialysis.

Animals↗

Role of efferent and afferent vagal nerve activity during reproduction: integrating function of oxytocin on metabolism and behaviour.

The vagal nerves convey information between the brain and the gastrointestinal tract in both afferent and efferent direction. The efferent vagal nerves regulate gastrointestinal secretory and motor function and also the activity in the endocrine system of the gut. Gastrointestinal function and anabolic metabolism is optimized during gestation and lactation as a means of saving energy for this calorie-demanding process. This enhanced activity seems to involve central oxytocinergic transmission which increases efferent vagal nerve activity as reflected by altered levels of gastrointestinal hormones in plasma. In parallel a behaviour pattern characterized by sedation is induced. In addition, vagal afferents transfer information from the gut to the brain, e.g. as to the presence or absence of calories in the gastrointestinal tract. It is well known that satiety and sedation following a meal is in part caused by an activation of vagal afferents in response to food intake. Cholecystokinin released from the intestine is one of the factors that triggers the afferent vagal nerve activity. Also reproductive "interactive behaviours" such as milk ejection and maternal behaviour can be induced by CCK via afferent activation of vagal nerves. In contrast, when no food reaches the gut, milk production and ejection is blocked. Parts of these effects are vagally mediated, since they can be observed in vagotomized rats receiving full amounts of calories.

Afferent Pathways↗

[Physiologic regulation of gastric acid secretion].

Physiological regulatory mechanisms of gastric acid secretion are the basis for all those studies which attempt to analyze the pathophysiological role of acid secretion. The major stimulus of parietal cell function is food intake which acts via activation of cephalic-vagal and gastric mechanisms. Cephalic phase of acid secretion is augmented predominantly by acetylcholine and gastrin while histamine is of major importance during the gastric phase. A contribution of neuropeptides located in the ex- and intrinsic nervous system such as enkephalin, beta-endorphin, gastrin-releasing peptide and neuromedin C ist most likely, however, their exact physiological role remains to be determined especially in man. Following maximal acid secretion parietal cell function is turned down which is paralleled by the decrease of intragastric pH. The mechanisms responsible for this effect originate in the stomach and small intestine. In contrast to the stimulatory factors the physiologically relevant inhibitors of acid secretion are less well known. Hormones such as somatostatin, glucagon-like peptide-1 (7-36)-NH2 and peptide YY are presumably of importance. The role of secretin, GIP, CCK and neurotensin is somewhat more controversial and remains to be examined in greater detail in humans. Especially the synergistic action of gastrointestinal hormones is virtually unknown. The increasing knowledge of the complex regulatory mechanisms in the stomach should result in new perspectives for the pathogenesis of peptic ulcer disease.

Animals↗

Hormonal changes after Roux-en Y gastric bypass for morbid obesity and the control of type-II diabetes mellitus.

Morbid obesity (MO) is associated with diabetes mellitus-type II (DM-II). Roux-en Y gastric bypass (RNY) has been shown to normalize glucose intolerance in these patients through an incompletely understood mechanism. Gastrointestinal hormonal changes have been suggested as an explanation for resolution of DM II. Preoperatively, 20 MO patients with DM-II were evaluated for demographics and fasting levels of the following: glucose, insulin, C-peptide, glucagon, cortisol, gastric inhibitory polypeptide (GIP), and glucagon-like peptide-1 (GLP-1). Each patient underwent RNY with a 15-cc gastric pouch and 150-cm Roux limb. Postoperatively, each of the variables was measured at 2 weeks, 6 weeks, and 12 weeks and compared with the preoperative result using Student t test with significance, P = 0.05. Results are expressed as mean +/- SD. Twenty patients (5 male and 15 female), age 40.3 +/- 7.9 years, weight 146.3 +/- 34.0 kg, height 158.7 +/- 18.7 cm, and BMI 52.7 +/- 8.8, were enrolled in this IRB-approved protocol. Weight and BMI decreased progressively (117.5 +/- 26.9 kg and 47.0 +/- 7.4, P = 0.01, respectively) during the study but reached significance only at 12 weeks. Fasting plasma glucose decreased significantly within 2 weeks after RNY. Insulin and cortisol both approached, but never achieved, significant changes over 12 weeks. GLP-1 increased initially, but not significantly. GIP and C-peptide both decreased significantly. Glucagon remained essentially unchanged over 12 weeks. RNY rapidly normalizes fasting plasma glucose in morbidly obese patients with DM-II. GIP, a gactor in the enteroinsulin axis, decreases and may play a role in the correction of DM-II after gastric bypass.

Adult↗

Glycerol release from incubated human adipocytes is not affected by gastrointestinal peptides.

There is evidence for involvement of gastrointestinal hormones in pathogenesis of obesity and reports on lipolytic activity in animals. The in vitro lipolytic activity of these hormones was tested in human adipocytes. Vasoactive intestinal polypeptide, glucagon, secretin, human gastrin I, gastrin releasing polypeptide, gastric inhibitory polypeptide, pancreatic polypeptide, motilin, bombesin, neurotensin, C-peptide, as well as cholecystokinin did not stimulate lipolysis significantly above basal. These results indicate that the involvement of these hormones in obesity in man might not be due to a direct lipolytic effect on the human adipocyte.

Adipose Tissue↗

Ontogeny of peptide-producing nerves and endocrine cells of the gastro-duodeno-pancreatic region.

The ontogeny of different types of endocrine cells and nerves producing different hormonal peptides was studied by immunocytochemistry. The data indicate that several endocrine cell types are more frequent in the foetal than in the adult gastro-duodeno-pancreatic region. Some cell types were found to show an over-lapping distribution. Such distributional over-laps were more frequent in foetuses and neonates than in adults. Both parallel and non-parallel patterns of development of endocrine cells and peptide-producing nerves were detected. Together with available information on the trophic effects of the gastrointestinal hormonal peptides these findings indicate that foetal and neonatal endocrine cells may participate in the regulation of growth and morphogenesis in the gastrointestinal tract.

Animals↗

The effects of gastrin, gastric inhibitory polypeptide, secretin, and the octapeptide of cholecystokinin upon immunoreactive somatostatin release by the perfused canine pancreas.

The effects of gastrin, gastric inhibitory polypeptide, secretin, and the octapeptide of pancreozymin-cholecystokinin on immunoreactive somatostatin release were studied in the isolated perfused dog pancreas. Gastrin at a concentration of 65 ng/ml and the octapeptide of pancreozymin-cholecystokinin at a concentration of 25 ng/ml produced a prompt, but transient statistically significant, twofold rise in mean somatostatin concentration. Secretion at a concentration of 0.3 U/ml and gastric inhibitory polypeptide concentration of 58 ng/ml produced a prompt two- to threefold rise in mean somatostatin release, which persisted throughout the perfusion period. With all four polypeptides the pattern of the somatostatin response resembled that of insulin. It appears that pancreatic somatostatin release is stimulated by gastrointestinal hormones that influence the secretion of insulin and glucagon.

Animals↗

Physiology and pathophysiology of gastrin: a review.

Recent advances in understanding the physiology and pathophysiology of the gastrointestinal hormone, gastrin, are reviewed. Details of gastrin biosynthesis, secretion, and cellular actions may have broad implications for other peptide hormones. Potentially useful antigastrin drugs are described. Areas of future development are suggested.

DNA Replication↗