Gastrointestinal peptide hormones as modulators of bile secretion.
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Animals↗
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Effects of hormones on gastrointestinal motility.
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Animals↗
Regulation of cholangiocyte bicarbonate secretion.
The objective of this review article is to discuss the role of secretin and its receptor in the regulation of the secretory activity of intrahepatic bile duct epithelial cells (i.e., cholangiocytes). After a brief overview of cholangiocyte functions, we provide an historical background for the role of secretin and its receptor in the regulation of ductal secretion. We review the newly developed experimental in vivo and in vitro tools, which lead to understanding of the mechanisms of secretin regulation of cholangiocyte functions. After a description of the intracellular mechanisms by which secretin stimulates ductal secretion, we discuss the heterogeneous responses of different-sized intrahepatic bile ducts to gastrointestinal hormones. Furthermore, we outline the role of a number of cooperative factors (e.g., nerves, alkaline phosphatase, gastrointestinal hormones, neuropeptides, and bile acids) in the regulation of secretin-stimulated ductal secretion. Finally, we discuss other factors that may also play an important role in the regulation of secretin-stimulated ductal secretion.
Animals↗
Hormonal responses to complete or hydrolyzed protein diets in patients after upper gastrointestinal surgery.
Six gastrointestinal hormones were measured in the plasma of six healthy controls and long-term changes were evaluated in six patients 2-20 years after upper gastrointestinal surgery. In a metabolic unit study we determined fasting hormonal levels, the time to peak hormonal response, and a 135-minute hormonal response to the meal. Test meals were isocaloric, 500 kcal, and isonitrogenous, consisting either of natural breakfast components or of complete liquid diets with intact protein (Ensure) or hydrolyzed protein (Vital). Postsurgical subjects were in good health and had no postcibal complaints. Nevertheless, their hemoglobin and serum albumin were significantly lower than in controls. Postsurgical subjects had higher fasting gastrin (121.3 +/- 11.6 vs 65.4 +/- 6.6 pg/ml, P less than .01) and motilin (148.7 +/- 32.9 vs 70.4 +/- 13.1 pg/ml, P less than .05) than controls. In postsurgical patients the peak gastrin and pancreatic glucagon responses to meals were obtained in significantly shorter time. Their total response to motilin and secretin to meals was significantly lower than in controls. Fasting glucose and the meal-induced responses of insulin and vasoactive intestinal polypeptide were not different from controls. The nature of dietary protein did not significantly affect hormonal responses to feeding. We conclude that gastrointestinal hormonal changes persist many years after surgery. These changes are probably related to faster transit of meals with a generally weaker total hormonal response to feeding. Although these differences from normal may be nutritionally well compensated, they may become important in periods of metabolic stress.
Adult↗
Biological determination of gastrointestinal peptide hormones.
Procedures for the determination of secretin, gastrin, cholecystokinin-pancreozymin, glucagon and villikinin in various species are reported. The sensitivities of the individual methods are dealt with.
Animals↗
Functional development of the human gastrointestinal tract: hormone- and growth factor-mediated regulatory mechanisms.
The present review focuses on the control of gastrointestinal (GI) tract development. The first section addresses the differences in general mechanisms of GI development in humans versus rodents, highlighting that morphogenesis of specific digestive organs and the differentiation of digestive epithelia occur not only at different stages of ontogeny but also at different rates. The second section provides an overview of studies from the author's laboratory at the Université de Sherbrooke pertaining to the development of the human fetal small intestine and colon. While both segments share similar morphological and functional characteristics, they are nevertheless modulated by distinct regulatory mechanisms. Using the organ culture approach, the author and colleagues were able to establish that hormones and growth factors, such as glucocorticoids, epidermal growth factor, insulin and keratinocyte growth factor, not only exert differential effects within these two segments, they can also trigger opposite responses in comparison with animal models. In the third section, emphasis is placed on the functional development of human fetal stomach and its various epithelial cell types; in particular, the glandular chief cells responsible for the synthesis and secretion of gastric enzymes such as pepsinogen-5 and gastric lipase. Bearing in mind that limitations of available cell models have, until now, greatly impeded the comprehension of molecular mechanisms regulating human gastric epithelial cell functions, the last section focuses on new human gastric epithelial cell models recently developed in the author's laboratory. These models comprise a novel primary culture system of human fetal gastric epithelium including, for the first time, functional chief cells, and human gastric epithelium cell lines cloned from the parental NCI-N87 strain. These new cells lines could serve important applications in the study of pathogenic action and epithelial regeneration.
Animals↗
[Effects of intracerebroventricular injections of thyrotropin releasing hormone on gastrointestinal propulsive motility in rats].
The effect of intracerebroventricular (ICV) injections of thyrotropin releasing hormone (TRH) on the propulsive motility of the gastrointestinal tract was examined in rats. The distance travelled by charcoal meal through the small intestine, measured in terms of percentage of its total length, was recorded as the index of propulsive motility. The results were as follows: (1) The propulsive distance of charcoal meal was significantly reduced in a dose-dependent manner after ICV injections of TRH (1 microgram/10 microliters, 5 micrograms/10 microliters or 10 micrograms/10 microliters) (P less than 0.01-0.001) The effects were abolished by injection of atropine (5 micrograms/10 microliters ICV). (2) The gastrointestinal propulsive motility decreased markedly (P less than 0.01) after injection of a larger dose of TRH (50 micrograms/100 g) into the hypodermis. The effects were not completely blocked by subcutaneous injections of propranolol (5 mg/kg). (3) No effects (P greater than 0.05) were found on the inhibition of gastrointestinal propulsive motility after ICV injections of regitine (2.5 mg/kg im, 50 micrograms/50 microliters ICV) or propranolol (5 mg/kg im, 50 micrograms/50 microliters ICV). The results indicate that TRH has an inhibitory effect on the propulsive motility of gastrointestinal tract, which may be mediated via the non-adrenergic inhibitory nerve of the vagal nerves.
Animals↗
Stimulatory actions of insulin-like growth factor-I and transforming growth factor-alpha on intestinal neurotensin and peptide YY.
Proliferation of the gastrointestinal mucosa is stimulated by the growth factors, insulin-like growth factor-I (IGF-I) and transforming growth factor-alpha (TGF-alpha), or the closely related epidermal growth factor (EGF), as well as the gastrointestinal hormones, gastrin, neurotensin (NT), and peptide YY (PYY). The stimulatory actions of these growth factors or gastrointestinal hormones on the gastrointestinal mucosa may be direct or mediated in part by gastrointestinal peptides or the growth factors, respectively. The purpose of these studies therefore was to examine the effects of IGF-I and TGF-alpha on stomach gastrin and intestinal NT and PYY gene expression [i.e. messenger RNA (mRNA), peptide levels] and secretion. Mice were given recombinant human IGF-I (3, 6 mg/kg BW/day x 14 days). Transgenic mice with the rat TGF-alpha gene linked to a metallothionein promoter were used as a model of chronic TGF-alpha excess. IGF-I and TGF-alpha did not affect gastrin gene expression. Steady-state intestinal NT and PYY mRNA and peptide levels were elevated in a dose-related manner by IGF. TGF-alpha also increased intestinal expression of NT and PYY peptide, but not mRNA levels. Basal serum levels of PYY were elevated by IGF-I and TGF-alpha. IGF-I and TGF-alpha did not increase intestinal chromogranin A (CGA) gene expression, a marker of endocrine cells, or the density of PYY-containing cells in the colon, indicating that the elevations in intestinal gut peptide gene expression by IGF-I and TGF-alpha are not due simply to an increased number of enteroendocrine cells. IV infusion of EGF also stimulated release of PYY in the dog. Together, these findings indicate that IGF-I and TGF-alpha may cause secretion of gut hormones and exert a major upregulatory influence on the regulation of intestinal peptide hormone homeostasis.
Animals↗
Synthesis of gastrointestinal peptide hormones.
Synthesis of gastrin, CCK-PZ-octapeptide sulphate ester and secretin, is dealt with in some detail. A gastrin synthesis developed by the author's team is also described. The synthesis of glucagon and caerulein is, though touched upon, but not discussed in any detail.
Cholecystokinin↗
The relationships between personality traits and plasma gastrin, cholecystokinin, somatostatin, insulin, and oxytocin levels in healthy women.
In earlier studies performed on a group of women with gastrointestinal symptoms, significant positive correlations between the gastrointestinal hormone gastrin and anxiety, and a negative correlation with socialization were obtained. These and other relationships were tested on 33 healthy women. A comprehensive and concise statistical model was used for the analysis of correlations between, on one hand, the levels of oxytocin and the gastrointestinal hormones gastrin, cholecystokinin, somatostatin and insulin, and, on the other hand, personality traits. Almost all explained variance of the hormone levels could be referred to three personality trait factors, Anxiety, Aggressive non-conformity, and Detachment. The statistical explanation of the gastrin level variance was most successful, the three personality trait factors explaining 48% of this variance. Gastrin "increased" Anxiety while reducing Aggressive non-conformity and Detachment. A similar pattern for insulin was also reliable. Considering general trends, the negative correlations between all hormones and Detachment are interesting. Present data suggest that there is a psychoendocrinological antithesis to the fight-flight individual, characterized by high activity in the sympathoadrenal system: these contrasting persons, with high levels of the gastrointestinal hormones gastrin and insulin, tend to be warm and caring and non-aggressive--but often not free from anxiety. We do not think that the demonstrated associations between hormone levels and personality traits implicate a direct causal relationship. They rather may mirror the activity of centrally acting or hypothalamic control systems which influence both behavioural and endocrine profiles.
Adult↗
Release of GI hormones in mother and infant by sensory stimulation.
It is well established that sensory stimulation is of great importance for the growth of and for the physiological and psychological development of infants. Supplementary sensory stimulation such as non-nutritive sucking and tactile stimulation has been shown to increase the growth rate and the maturation of premature infants. In human neonates non-nutritive sucking has a vagally mediated influence on the levels of some gastrointestinal hormones. In animal experiments afferent electrical stimulations of the sciatic nerves at low intensity leads to an activation of the vagal nerves and to a consequent release of vagally controlled gastrointestinal hormones such as gastrin and cholecystokinin. We therefore assume that both non-nutritive sucking and tactile stimulation trigger the activity of sensory nerves which leads to a release of vagally regulated gut hormones. Since gut hormones stimulate gastrointestinal motor and secretory activity and the growth of the gastrointestinal tract, and enhance the glucose-induced insulin release, they may contribute to the beneficial effects on maturation and growth caused by sensory stimulation. In the breast-feeding situation, the sucking of the child elicits similar reflexes in the mother leading to an activation of the maternal gut endocrine system and a consequent increase in energy uptake. These data indicate that many types of neurogenic reflexes induced in mother-infant interactions are of importance for the energy economy of both mother and child.
Female↗
Effect of hormone therapy on the enteroinsular axis.
OBJECTIVE: Menopause is associated with a decline in insulin response to glucose and with insulin resistance. It has been proven that hormone therapy (HT) improves carbohydrate metabolism in postmenopausal women. However, it is known that gastrointestinal hormones play a key role in the coordination of digestion and absorption of ingested nutrients and in the regulation of pancreatic endocrine function. Therefore, the aim of this study was to investigate the effect of HT on gastrointestinal hormones and carbohydrate metabolism in postmenopausal women. DESIGN: The prospective study was performed in 90 healthy postmenopausal women (mean age 54.5 years, standard deviation 3.34 years), of whom 49 completed the study. They were randomized and treated either with continuous transdermal HT (0.05 mg 17[beta]-estradiol every 24 hours) combined with 5 mg oral dydrogesterone daily (group A, n = 25), or with oral HT (2 mg 17[beta]-estradiol semihydrate every 24 hours) combined with 10 mg dydrogesterone as a continuous therapy (group B, n = 8). The control group (group C, n = 16) received no HT. Both basal and meal-stimulated plasma concentrations of glucose, insulin, glucose-dependent insulinotropic peptide (GIP), glucagon-like peptide-1 (GLP-1), and cholecystokinin (CCK), as well as basal estrogen levels, were measured before HT and after 6 and 12 months of treatment. At the same time intervals, all the studied parameters were measured for group C. RESULTS: After 12 months of the transdermal HT, a decrease in both fasting (P < 0.002) and postprandial (P < 0.05) plasma glucose levels was observed. Oral HT reduced only the fasting plasma glucose level in the 12th month of treatment (P < 0.05). Regardless of the route of administration, HT reduced postprandial plasma levels of insulin (oral HT: P < 0.05; transdermal HT: P < 0.02). Fasting plasma levels of GIP were reduced after 6 and 12 months of transdermal HT (P < 0.002 and P < 0.001, respectively). Moreover, levels of postprandial GIP were reduced after 6 and 12 months of transdermal HT (P < 0.002 in both cases). Fasting and postprandial GLP-1 levels were reduced by transdermal HT after 12 months of supplementation. Oral HT also decreased these levels, but not significantly. The observed differences may, however, be related not only to the route of administration, but also to the difference in the dose of estradiol. Regardless of the route of administration, HT did not influence plasma levels of CCK. CONCLUSIONS: Hormone therapy significantly influences the enteroinsular axis in postmenopausal women and contributes to the normalization of plasma glucose levels.
Administration, Cutaneous↗
The influence of potato fibre on exocrine pancreatic secretions and on plasma levels of insulin, secretin and cholecystokinin in growing pigs.
The effect of a potato fibre preparation on exocrine pancreatic secretions and on gastrointestinal hormone levels in plasma was studied in three 8 weeks old piglets that were surgically fitted with a jugular vein catheter for blood sampling, a pancreatic duct catheter and a T-shaped duodenal cannula for collection of pancreatic juice. The animals were fed for 2 weeks a control diet (experimental period 1), thereafter for 2 weeks the control diet supplemented with 2% potato fibre (experimental period 2) and for another 2 weeks the control diet again (experimental period 3). Additionally, intraduodenal (i.d.) infusions of the experimental diet, the control diet and potato fibre as well as i.v. infusions of a solution containing cholecystokinin (CCK) and secretin were administered. Potato fibre in the diet evoked in tendency an increase in the volume of secretion of pancreatic juice and a significant increase both in the mean values of the total protein content and total activities of lipase, trypsin and alpha-amylase when compared to the control diet. The i.d. infusion of the control diet, experimental diet and fibre infusate as well as the i.v. administration of the hormone infusate led to a spontaneous secretory response of the exocrine pancreas. Besides gastrointestinal hormones, such as CCK, other factors such as short chain fatty acids may be involved in the regulation of the exocrine pancreas.
Animals↗
Metabolism of the gastrointestinal peptide hormones.
Results of investigations on the metabolism of gastrin, pentagastrin, cholecystokinin and secretin are discussed on the basis of data in the literature. Own results concerning the metabolism of 14C-pentagastrin are also described, out of which the significance of a biologically inactive metabolite is emphasized. This metabolite can be demonstrated in the circulation, and is excreted in the urine. As judged from the present state of investigations, this metabolite has a crucial importance in the metabolism of pentagastrin.
Animals↗
The neural crest and the origin of the insulin-producing and other gastrointestinal hormone-producing cells.
It has been proposed that the endocrine cells of the digestive tract derive from the neuroectoderm (neural crest). To test this hypothesis we removed the entire ectoderm, the precursor of the neural crest, of embryonic rats prior to the formation of the neural crest and cultured the mesoendoderm for 11 days. In every case where a pancreas developed, insulin was detected or B cells were observed. Thus, a neural crest origin for these cells is eiliminated.
Amines↗
Importance of the duodenal passage and pouch volume after total gastrectomy and reconstruction with the Ulm pouch: prospective randomized clinical study.
The objective of this randomized study was to examine which reconstruction method and which pouch volume offer the best preconditions for a good quality of life and extensive physiologic regulation of gastrointestinal hormones after total gastrectomy. Up to now there is no general agreement with regard to the ideal reconstruction after total gastrectomy. The importance of the duodenal passage, the need for a pouch reconstruction, and the ideal pouch volume are matters of controversy. A total of 60 patients underwent the following reconstructions: Ulm pouch (pouch reconstruction with preservation of the duodenal passage), Hunt-Lawrence-Rodino pouch, or Roux-en-Y reconstruction without pouch. The clinical course, quality of life, and regulation of gastrointestinal hormones in correlation to reconstruction type and pouch volume were documented. Quality of life was assessed by means of a standardized specific questionnaire. Blood glucose, insulin, cholecystokinin, motilin, secretin, and pancreatic polypeptide were measured after stimulation by a standardized test meal. Six months after total gastrectomy those patients with an Ulm pouch were found to have a significantly better life quality (p < 0.01), higher body weight, and better physiologic regulation of gastrointestinal hormones; moreover, they developed (in contrast to all other reconstruction types) no pathologic glucose tolerance. Our conclusion is that all patients with a postoperative life expectancy of at least 6 months (i.e., tumor stages UICC I and II) should undergo pouch reconstruction with preservation of the duodenal passage.
Aged↗
[Effect of corticosterone, glucagon and growth hormone on gastrointestinal propulsive motility in rats (author's transl)].
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Animals↗
Gastric emptying and orocecal transit time in pregnancy.
PURPOSE: To evaluate the effects of pregnancy on gastrointestinal function, we determined gastric emptying time, orocecal transit time, and fasting gastrointestinal hormone levels (cholecystokinin, gastrin, pancreatic polypeptide, neurotensin) in 11 women with mild dyspeptic symptoms during the first and third trimesters of their pregnancies, and again 4-6 months after delivery. METHODS: After the women ingested a disaccharide solution, orocecal transit time was determined by monitoring breath hydrogen concentrations at 10-min intervals, and values were compared with the postpartum value. Ultrasound examinations of gastric emptying were performed during the same intervals. RESULTS: The half-emptying time and the final gastric emptying time did not differ in the first and third trimesters and postpartum, but gastrointestinal transit time was significantly longer in the third trimester of pregnancy than postpartum (100.0 min [range, 50.5-240.0 min] vs 70.0 min [range, 40.5-240.0 min; P < 0.05]), respectively. Mean plasma pancreatic polypeptide values were lower in the third trimester of pregnancy than postpartum. and a negative correlation was observed between pancreatic polypeptide levels and transit time in the third trimester (r = -0.65; P = 0.0261). The plasma levels of other gastrointestinal hormones did not differ in the various periods studied. CONCLUSIONS: Our study shows that, despite evident dyspeptic symptoms, there were no significant alterations in gastric emptying or orocecal transit time during the first trimester of pregnancy. Conversely, in the third trimester, orocecal transit time was significantly longer.
Adult↗