Release Of Gastrointestinal Hormones Research Articles

Intraduodenal protein modulates antropyloroduodenal motility, hormone release, glycemia, appetite, and energy intake in lean men

Intraduodenal fat and carbohydrate modulate antropyloroduodenal motility and hormone release and suppress appetite and energy intake in a load-dependent manner. Protein also suppresses energy intake, but its effects on these gastrointestinal factors and their role in the appetite-suppressive effects of protein remain unclear. We aimed to characterize the effects of different intraduodenal protein loads on antropyloroduodenal pressures, gastrointestinal hormone release, glucose and insulin concentrations, appetite perceptions, and energy intake. Sixteen lean, healthy men were studied on 4 occasions in a randomized, double-blind fashion. Antropyloroduodenal pressures, plasma glucagon-like peptide 1 (GLP-1), cholecystokinin, peptide YY, ghrelin, blood glucose, serum insulin, and appetite were measured during 60-min, 4-mL/min intraduodenal infusions of protein at 0.5, 1.5, or 3 kcal/min or saline (control). Energy intakes at a buffet lunch consumed immediately after the infusion were quantified. Increases in the load of protein resulted in greater suppression of antral motility, greater stimulation of basal and isolated pyloric pressures and plasma cholecystokinin and GLP-1 concentrations, and greater suppression of energy intake. However, energy intake was reduced only after a protein load of 3 kcal/min compared with after all other treatments (P < 0.05). The suppression of energy intake after adjustment for cholecystokinin, GLP-1, and insulin was related inversely with basal pyloric pressure (r = -0.51, P < 0.001). The acute effects of intraduodenal protein on antropyloroduodenal motility, gastrointestinal hormone release, glucose, and insulin are load dependent and contribute to the suppression of energy intake. This trial was registered at www.anzctr.org.au as 12610000376044.

Effects of Long- and Short-Chain Fatty Acids on the Release of Gastrointestinal Hormones using an ex Vivo Porcine Intestinal Tissue Model

Gastrointestinal (GI) peptide hormones play an important role in short-term regulation of food intake and blood glucose levels. Modulating their release is of potential relevance for weight management and possibly diabetes. As currently available models are hard to extrapolate to the human situation, the use of porcine intestinal tissue, collected from slaughter pigs, was investigated for this purpose. Intestinal tissue disks showed a predicted regional release pattern of GI peptides. Various long-chain fatty acids differentially stimulated release of glucagon-like peptide 1 (GLP-1) (up to 500%) and glucagon-like peptide 2 (GLP-2) (up to 200%) from ileal tissue disks, but effects on peptide YY (PYY) did not reach significance. Short-chain fatty acids had no effects on the release of GLP-1, GLP-2, and PYY in either the ileum or colon. In conclusion, this porcine tissue model shows to be of advantageous use in a tiered approach to study the potential of satiety-inducing compounds to be selected for studies in humans.

Gum chewing as a strategy to reduce the duration of postoperative ileus

Postoperative ileus is a common complication following surgery. Many pharmacological agents and surgical techniques have been proposed to influence the severity and duration of an ileus; however, no individual method has been shown to successfully influence its clinical course. Often, these techniques are used in combination to create a ‘fast-track’ recovery program. Current research has proposed gum chewing as a form of sham feeding that can be used as an alterative to early oral feedings. In this article, Caroline Lafon and Dr Lauren Lawson will review recent randomized controlled trials and meta-analyses studying the effects of gum chewing on gastrointestinal motility. Research suggests that gum chewing is a safe and cost-effective method that acts by stimulating the cephalic-vagal system, triggering the release of gastrointestinal hormones and juices, increasing salivation and pancreatic juice release, and ultimately promoting the return of normal bowel function. Gum chewing can be used as a component in a fast-track recovery program to reduce the duration of postoperative ileus and thereby reduce hospital length of stay and hospital costs.

Somatostatin receptor SPECT

Somatostatin is a peptide with a broad distribution in the nervous system and acts as a neurotransmitter in several organs, having a wide range of mainly inhibiting effects, such as the suppression of growth hormone release, as well as the inhibition of pancreatic and gastrointestinal hormone release. Five somatostatin receptor subtypes have been cloned and demonstrated to have an emphasized expression in all human tumours. In particular, type 2 receptors were identified as the most frequently represented on the surface of neuroendocrine tumour cells, providing the molecular basis for many clinical applications of somatostatin analogues. Towards the end of the 1980s, the in vivo demonstration of somatostatin receptors on the surface of some tumours raised interest in receptor imaging, and indeed the peptide receptor overexpression on tumour cells, as compared to normal tissues, constitutes the basis for molecular imaging of these tumours. This review intends to illustrate the development of single photon emission radiopharmaceuticals for the study of somatostatin receptors and their application in diagnostic imaging.

Remission of type 2 diabetes mellitus following bariatric surgery: review of mechanisms and presentation of the concept of ‘reversibility’

Roux-en-Y gastric bypass (RYGB) leads to remission of type 2 diabetes mellitus (T2DM) in a majority of patients. This is prompting investigation of RYGB, and other bariatric operations as interventional therapies for T2DM. The impact of RYGB is due to an increase in the release of gastrointestinal hormones in response to a meal [glucagon-like peptide, peptide YY, oxyntomodulin]. This effect involves the parasympathetic nervous system. These same hormones are responsible for an early increase in β-cell secretion of insulin, leading to early remission of T2DM following RYGB. Progressive weight loss leads to a later improvement in peripheral insulin sensitivity, which is required for later remissions, and is responsible for re-emergence of T2DM in individuals who regain weight in long-term follow-up. As the success of bariatric surgery has prompted the emergence of the concept that T2DM is reversible, we offer a theory to predict reversibility of diabetes after bariatric surgery that is based on baseline beta cell function. This review will improve the understanding of the physiology of bariatric surgery and its impact on T2DM, stimulate investigations into new avenues to treat T2DM, and allow better selection of nonobese individuals for interventional therapy of T2DM.

Intracoronary gastrin 17 increases cardiac perfusion and function through autonomic nervous system, CCK receptors, and nitric oxide in anesthetized pigs

The release of gastrointestinal hormones has been reported to modulate reflex cardiovascular responses caused by gastric distension, although the role played by gastrin 17 is as yet unknown. The present study was therefore planned to determine the primary in vivo effect of gastrin 17 on coronary blood flow and cardiac function and the involvement of autonomic nervous system, CCK1/2 receptors, and nitric oxide (NO). In 40 anesthetized pigs, gastrin 17 was infused into the left anterior descending coronary artery at constant heart rate and arterial blood pressure. In 35 of the 40 pigs, the mechanisms of the observed hemodynamic responses were analyzed by repeating gastrin 17 infusion after autonomic nervous system and NO blockade, and after specific CCK receptors agonists/antagonists administration. Intracoronary gastrin 17 administration caused dose-related increases of both coronary blood flow and cardiac function. The intracoronary co-administration of CCK33/pentagastrin and gastrin 17 potentiated the coronary effects observed when the above agents were given alone (P <0.05). The potentiation of the cardiac response was observed only with the co-administration of pentagastrin and gastrin 17 (P <0.05). Moreover, blockade of muscarinic cholinoceptors (intravenous atropine) and of α-adrenoceptors (intravenous phentolamine) did not abolish the hemodynamic responses to gastrin 17. The cardiac and vascular effects of the hormone were prevented by blockade of β-adrenoceptors (intravenous atenolol and butoxamine), CCK1/2 receptors (intracoronary lorglumide and CAM-1028), and NO synthase (intracoronary Nω-nitro-l-arginine methyl ester). In conclusion, gastrin 17 primarily increased coronary blood flow and cardiac function through the involvement of CCK receptors, β-adrenoceptors, and NO release.

Deficits in gastrointestinal responses controlling food intake and body weight

The gastrointestinal tract serves as a portal sensing incoming nutrients and relays mechanical and chemosensory signals of a meal to higher brain centers. Prolonged consumption of dietary fat causes adaptive changes within the alimentary, metabolic, and humoral systems that promote a more efficient process for energy metabolism from this rich source, leading to storage of energy in the form of adipose tissue. Furthermore, prolonged ingestion of dietary fats exerts profound effects on responses to signals involved in termination of a meal. This article reviews the effects of ingested fat on gastrointestinal motility, hormone release, and neuronal substrates. It focuses on changes in sensitivity to satiation signals resulting from chronic ingestion of high-fat diet, which may lead to disordered appetite and dysregulation of body weight.

Octreotide

Octreotide

Roles of Short-Chain Fatty Acids and their Receptors in Colonic Motility

Short chain fatty acids (SCFAs) are major anions in the large intestine. They are produced by bacterial fermentation of dietary fiber. However, the mechanism by which intraluminal SCFAs are sensed is unknown. Free fatty acids including SCFAs have recently been demonstrated to act as ligands for several G-protein-coupled receptors (GPCRs: FFA1, FFA2, FFA3, GPR84, GPR109A and GPR120). SCFAs are ligands for FFA2 and FFA3. These receptors are proposed to play a variety of physiological and pathophysiological roles in the intestine. In rat and human colons, FFA2 and/or FFA3 are located in mucosal enteroendocrine cells containing peptide YY (PYY) and are related to energy balance. Among SCFAs, propionate and butyrate induce concentration-dependent phasic and tonic contractions in rat colonic circular muscle. These responses are not observed in mucosal free preparations. Thus, FFA2 and FFA3 are important molecular devices for monitoring the chemical composition in the colonic lumen. For the local function of SCFAs, it should be stressed that individual SCFAs have different modes of action on colonic smooth muscles. These different actions may be due to the relative contributions of FFA2 and FFA3 to the control of intestinal muscle activity. FFA2 and FFA3 may also contribute to the whole body energy balance through the release of gastrointestinal hormones related to feeding and satiety control. This review summarizes recent findings about the roles of deorphanized FFA receptors, especially, FFA2 and FFA3 and their contributions to the regulation of colonic motility.

Pathophysiology, diagnosis and management of postoperative dumping syndrome

Dumping syndrome is a frequent complication of esophageal, gastric or bariatric surgery. Rapid gastric emptying, with the delivery to the small intestine of a significant proportion of solid food as large particles that are difficult to digest, is a key event in the pathogenesis of this syndrome. This occurrence causes a shift of fluid from the intravascular component to the intestinal lumen, which results in cardiovascular symptoms, release of several gastrointestinal and pancreatic hormones and late postprandial hypoglycemia. Early dumping symptoms comprise both gastrointestinal and vasomotor symptoms. Late dumping symptoms are the result of reactive hypoglycemia. Besides the assessment of clinical alertness and endoscopic or radiological imaging, a modified oral glucose tolerance test might help to establish a diagnosis. The first step in treating dumping syndrome is the introduction of dietary measures. Acarbose can be added to these measures for patients with hypoglycemia, whereas several studies advocate guar gum or pectin to slow gastric emptying. Somatostatin analogs are the most effective medical therapy for dumping syndrome, and a slow-release preparation is the treatment of choice. In patients with treatment-refractory dumping syndrome, surgical reintervention or continuous enteral feeding can be considered, but the outcomes of such approaches are variable.

Taking the Lag out of Jet Lag through Model-Based Schedule Design

Travel across multiple time zones results in desynchronization of environmental time cues and the sleep–wake schedule from their normal phase relationships with the endogenous circadian system. Circadian misalignment can result in poor neurobehavioral performance, decreased sleep efficiency, and inappropriately timed physiological signals including gastrointestinal activity and hormone release. Frequent and repeated transmeridian travel is associated with long-term cognitive deficits, and rodents experimentally exposed to repeated schedule shifts have increased death rates. One approach to reduce the short-term circadian, sleep–wake, and performance problems is to use mathematical models of the circadian pacemaker to design countermeasures that rapidly shift the circadian pacemaker to align with the new schedule. In this paper, the use of mathematical models to design sleep–wake and countermeasure schedules for improved performance is demonstrated. We present an approach to designing interventions that combines an algorithm for optimal placement of countermeasures with a novel mode of schedule representation. With these methods, rapid circadian resynchrony and the resulting improvement in neurobehavioral performance can be quickly achieved even after moderate to large shifts in the sleep–wake schedule. The key schedule design inputs are endogenous circadian period length, desired sleep–wake schedule, length of intervention, background light level, and countermeasure strength. The new schedule representation facilitates schedule design, simulation studies, and experiment design and significantly decreases the amount of time to design an appropriate intervention. The method presented in this paper has direct implications for designing jet lag, shift-work, and non-24-hour schedules, including scheduling for extreme environments, such as in space, undersea, or in polar regions.

Can Gum Chewing Reduce Postoperative Ileus after Open Abdominal Surgery?

Purpose: Gum chewing activates chephalic-vagal reflex as in food consumption and increases the release of gastrointestinal hormones which are related with gut motility. The objective of this study was to assess whether it is effective in shortening the time of hospitalization and postoperative ileus. Methods: Twenty patients who received open abdominal surgery for colon cancer in Gachon University, Gil Hospital were collected. They were further categorized to gum-chewing group (n=10, mean age=52.0 years, range 37 to 70) and control group (n=10, mean age=59.7 years, range 35 to 75) randomly. The patients in the gum-chewing group chewed gum three times a day from the first postoperative AM until the day they began oral intake. The time of gas out was recorded in each group. Results: The mean time of gas out were 2.35 days (SD 1.2) in gum-chewing group and 2.87 days (SD 1.2) in control group (P=0.41). The mean postoperative hospital days were 10.5 days in gum-chewing group and 13.0 days in control group (P=0.23). Conclusion: There were no statistically significant results for shortnening of postoperative ileus and hospital day in this study.

The clinical significance of gastrointestinal changes with aging

With the graying of the world's population, there is an increased interest in the physiological effects of aging. This review examines the physiological changes of the gut with aging and their clinical significance. Changes with aging in the gastrointestinal tract are variable, but in some cases they are responsible for a variety of symptoms. Thus, alterations in taste and smell, gastric motility, intestinal overgrowth and changes in gastrointestinal hormone release are the basis of the physiological anorexia of aging. Alterations in swallowing lead to silent aspiration. Changes in gastric emptying play a role in postprandial hypotension. Changes in gastrointestinal function can lead to constipation and fecal incontinence. Weakening of the colonic muscular wall produces diverticula. Achlorhydria is associated with malabsorption of some forms of iron and calcium. Vitamin D malabsorption aggravates the hypovitaminosis D that is so common in older persons. Changes in probiotics can lead to diarrhea and altered immune system. In the liver, aging is associated with delayed drug metabolism. Changes in the physiology of the gut play a role in the anorexia of aging, aspiration pneumonia, postprandial hypotension, constipation and fecal incontinence.

Reproducibility of energy intake, gastric emptying, blood glucose, plasma insulin and cholecystokinin responses in healthy young males

Gastric emptying, as well as intragastric meal distribution, and gastrointestinal hormones, including cholecystokinin (CCK), play an important role in appetite regulation. The evaluation of gastrointestinal factors regulating food intake is commonly performed in healthy, lean, young male participants. It has, however, been suggested that there is a marked interindividual variability in the effects of nutrient 'preloads' on energy intake in this group. Whether there is significant intraindividual variation in acute energy intake after a nutrient preload, and, if so, how this relates to day-to-day differences in gastric emptying and gastrointestinal hormone release, is unclear. The purpose of the present paper is to evaluate the hypothesis that energy intake after a nutrient preload would be reproducible and associated with reproducible patterns of gastric emptying, intragastric distribution and gastrointestinal hormone release. Fifteen healthy men (age 25 (sem 5) years) consumed a glucose preload (50 g glucose in 300 ml water; 815 kJ) on three occasions. Gastric emptying and intragastric meal distribution (using three-dimensional ultrasound), blood glucose, plasma insulin and CCK concentrations and appetite perceptions were evaluated over 90 min, and energy intake from a cold buffet-style meal was then quantified. Energy intake was highly reproducible within individuals between visits (intraclass correlation coefficient, ri = 0.9). Gastric emptying, intragastric meal distribution, blood glucose, plasma insulin and CCK concentrations and appetite perceptions did not differ between visits (ri>0.7 for all). In healthy males, energy intake is highly reproducible, at least in the short term, and is associated with reproducible patterns of gastric emptying, glycaemia, insulinaemia and CCK release.

The effect of salatrim, a low-calorie modified triacylglycerol, on appetite and energy intake

BackgroundSalatrim is modified triacylglycerol that is rich in short-chain fatty acids and stearic acid. It is used as a lower-calorie fat replacer. In addition, it has been hypothesized that salatrim's reduced absorption in the small intestine may lead to greater amounts of fat in the gastrointestinal tract, which may decrease appetite and energy intake through the release of appetite-regulating gastrointestinal hormones. ObjectiveWe aimed to compare the effects of salatrim and traditional fat on appetite, ad libitum energy intake, and gastrointestinal hormones. DesignTwenty-two healthy, young, normal-weight men participated in a randomized, double-blind, crossover study. Test meals were a traditional fat meal and a salatrim meal with a mixture of traditional fat and salatrim. Visual analogue scales were used to record appetite and well-being every 30 min, and blood was sampled frequently. An ad libitum lunch was served 4.5 h after the test meal. ResultsThe salatrim meal increased fullness (P = 0.04) and decreased hunger (P = 0.06) significantly more than did the traditional fat meal. The traditional fat meal increased well-being (P = 0.02). There was no significant difference in ad libitum energy intake or overall energy intake between the 2 test days. No significant differences in blood glucose, insulin, triacylglycerol, ghrelin, cholecystokinin, glucagon-like peptide-1, or peptide YY concentrations were found. A significantly (P = 0.01) smaller increase in free fatty acids was observed after the salatrim meal than after the traditional fat meal. ConclusionsSalatrim had a modestly more suppressive effect on appetite than did a traditional fat. Gastrointestinal hormones did not seem to be involved.

Minimal enteral nutrition

Although parenteral nutrition has been used widely in the management of sick very low birth weight infants, a smooth transition to the enteral route is most desirable. Trophic feeding is the practice of feeding small volume of enteral feeds in order to stimulate the development of the immature gastrointestinal tract of the preterm infant. This practice has also been termed as minimal enteral nutrition (MEN). MEN improves gastrointestinal enzyme activity, hormone release, blood flow, motility and microbial flora. Clinical benefits include improved milk tolerance, greater postnatal growth, reduced systemic sepsis and shorter hospital stay. There is currently no evidence of any adverse effects following MEN. MEN can be commenced in neonates on ventilation and total parenteral nutrition. A protocol of giving MEN has been presented here.

Efeitos do exercício físico sobre o trato gastrintestinal

O impacto do exercício sobre o trato gastrintestinal (TGI), apesar de pouco investigado, é uma área de grande interesse. O exercício aeróbio intenso e de longa duração pode provocar sintomas gastrintestinais. Estes podem ser divididos em sintomas superiores (vômitos, náuseas e pirose retroesternal - azia) e inferiores (diarréia, cólica abdominal, perda de apetite, sangramento, aceleração dos movimentos intestinais e vontade de defecar). A etiologia desses sintomas durante o exercício é multifatorial e inclui a redução do fluxo sanguíneo intestinal, a liberação de hormônios gastrintestinais, o estresse mecânico sobre o TGI, a desidratação, os fatores psicológicos, a idade, o sexo, a dieta e o nível de treinamento do indivíduo. Por outro lado, o exercício de baixa intensidade tem efeito protetor sobre o TGI, principalmente com relação à predisposição a certas doenças como o câncer de cólon, a diverticulite, a colelitíase e a constipação. Diversos mecanismos são postulados para explicar os efeitos do exercício sobre o TGI, contribuindo para o desenvolvimento de estratégias terapêuticas no tratamento de indivíduos com sintomas e doenças gastrintestinais.

Modulation by high-fat diets of gastrointestinal function and hormones associated with the regulation of energy intake: implications for the pathophysiology of obesity

The presence of fat in the small intestine slows gastric emptying, stimulates the release of many gastrointestinal hormones, and suppresses appetite and energy intake as a result of the digestion of fats into free fatty acids; the effects of free fatty acids are, in turn, dependent on their chain length. Given these effects of fat, it is paradoxical that high dietary fat intakes have been linked to increased energy intake and body weight and are considered to play a significant role in the pathogenesis of obesity. However, increasing evidence indicates that a chronic increase in dietary fat is associated with an attenuation of the feedback signals arising from the small intestine induced by fat, with a consequent relative acceleration of gastric emptying, modulation of gastrointestinal hormone secretion, and attenuation of the suppression of energy intake. This review addresses the gastrointestinal factors involved in the regulation of appetite and energy intake, with a particular focus on 1) the gastrointestinal mechanisms triggered by small intestinal fat that modulate energy intake, 2) the potential role of a high dietary fat intake in the development of obesity, and 3) implications for the prevention and management of obesity.

Free Fatty Acids Have More Potent Effects on Gastric Emptying, Gut Hormones, and Appetite Than Triacylglycerides

The effects of fat on gastric emptying (GE), gut hormones, and energy intake are dependent on digestion to free fatty acids (FFAs). In animals, small intestinal oleic acid inhibits energy intake more potently than the triacylglyceride (TG) triolein, but there is limited information about the comparative effects of FFA and TG in human beings. We compared the effects of FFA and TG on GE, gut hormone secretion, appetite, and energy intake in healthy males. Nine men (age, 23 +/- 2 y; body mass index, 22 +/- 1 kg/m(2)) were studied on 3 occasions to evaluate the effects of (1) 40 g oleic acid (FFA, 1830 kJ), (2) 40 g macadamia oil (TG, 1856 kJ; both 600-mL oil-in-water emulsions stabilized with 4% milk protein and labeled with 15 MBq (123)I), or (3) 600 mL 4% milk protein (control, 352 kJ), administered intragastrically, on GE, plasma cholecystokinin (CCK) and peptide-YY (PYY) levels, appetite perceptions, and subsequent energy intake. GE of FFA was much slower than that of TG (P < .05), with greater retention of FFA, than TG, in the proximal stomach (P < .001). Hunger was less (P < .05), and fullness was greater (P < .05), after FFA when compared with control and TG. Increases in plasma CCK and PYY levels were greater after FFA than TG or control (P < .05). Energy intake tended to be less after FFA compared with TG (control, 4754 +/- 610 kJ; TG, 5463 +/- 662 kJ; FFA, 4199 +/- 410 kJ). FFAs empty from the stomach more slowly, but stimulate CCK and PYY and suppress appetite more potently than TG in healthy human beings.

Load-dependent effects of duodenal glucose on glycemia, gastrointestinal hormones, antropyloroduodenal motility, and energy intake in healthy men

Gastric emptying is a major determinant of glycemia, gastrointestinal hormone release, and appetite. We determined the effects of different intraduodenal glucose loads on glycemia, insulinemia, glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP) and cholecystokinin (CCK), antropyloroduodenal motility, and energy intake in healthy subjects. Blood glucose, plasma hormone, and antropyloroduodenal motor responses to 120-min intraduodenal infusions of glucose at 1) 1 ("G1"), 2) 2 ("G2"), and 3) 4 ("G4") kcal/min or of 4) saline ("control") were measured in 10 healthy males in double-blind, randomized fashion. Immediately after each infusion, energy intake at a buffet meal was quantified. Blood glucose rose in response to all glucose infusions (P < 0.05 vs. control), with the effect of G4 and G2 being greater than that of G1 (P < 0.05) but with no difference between G2 and G4. The rises in insulin, GLP-1, GIP, and CCK were related to the glucose load (r > 0.82, P < 0.05). All glucose infusions suppressed antral (P < 0.05), but only G4 decreased duodenal, pressure waves (P < 0.01), resulted in a sustained stimulation of basal pyloric pressure (P < 0.01), and decreased energy intake (P < 0.05). In conclusion, variations in duodenal glucose loads have differential effects on blood glucose, plasma insulin, GLP-1, GIP and CCK, antropyloroduodenal motility, and energy intake in healthy subjects. These observations have implications for strategies to minimize postprandial glycemic excursions in type 2 diabetes.