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United European Gastroenterology Journal Jul 2021Different peripheral pathways are implicated in the regulation of the food ingestion-digestion cycle. (Review)
Review
BACKGROUND
Different peripheral pathways are implicated in the regulation of the food ingestion-digestion cycle.
METHODS
Narrative review on gastrointestinal mechanisms involved in satiety and hunger signalling.
RESULTS
Combined mechano- and chemoreceptors, peripherally released peptide hormones and neural pathways provide feedback to the brain to determine sensations of hunger (increase energy intake) or satiation (cessation of energy intake) and regulate the human metabolism. The gastric accommodation reflex, which consists of a transient relaxation of the proximal stomach during food intake, has been identified as a major determinant of meal volume, through activation of tension-sensitive gastric mechanoreceptors. Motilin, whose release is the trigger of gastric Phase 3, has been identified as the major determinant of return of hunger after a meal. In addition, the release of several peptide hormones such as glucagon-like peptide 1 (GLP-1), cholecystokinin as well as motilin and ghrelin contributes to gut-brain signalling with relevance to control of hunger and satiety. A number of nutrients, such as bitter tastants, as well as pharmacological agents, such as endocannabinoid receptor antagonists and GLP-1 analogues act on these pathways to influence hunger, satiation and food intake.
CONCLUSION
Gastrointestinal mechanisms such as gastric accommodation and motilin release are key determinants of satiety and hunger.
Topics: Animals; Cholecystokinin; Gastrointestinal Tract; Ghrelin; Glucagon-Like Peptide 1; Humans; Hunger; Motilin; Myoelectric Complex, Migrating; Satiation; Taste
PubMed: 34153172
DOI: 10.1002/ueg2.12097 -
Current Opinion in Gastroenterology Nov 2016The present review summarizes the past year's literature, both clinical and basic science, regarding neuroendocrine and intracellular regulation of gastric acid... (Review)
Review
PURPOSE OF REVIEW
The present review summarizes the past year's literature, both clinical and basic science, regarding neuroendocrine and intracellular regulation of gastric acid secretion and proper use of antisecretory medications.
RECENT FINDINGS
Gastric acid kills microorganisms, modulates the gut microbiome, assists in digestion of protein, and facilitates absorption of iron, calcium, and vitamin B12. The main stimulants of acid secretion are gastrin, released from antral G cells; histamine, released from oxyntic enterochromaffin-like cells; and acetylcholine, released from antral and oxyntic intramural neurons. Other stimulants include ghrelin, motilin, and hydrogen sulfide. The main inhibitor of acid secretion is somatostatin, released from oxyntic and antral D cells. Glucagon-like peptide-1 also inhibits acid secretion. Proton pump inhibitors (PPIs) reduce acid secretion and, as a result, decrease somatostatin and thus stimulate gastrin secretion. Although considered well tolerated drugs, concerns have been raised this past year regarding associations between PPI use and kidney disease, dementia, and myocardial infarction; the quality of evidence, however, is very low.
SUMMARY
Our understanding of the physiology of gastric secretion and proper use of PPIs continues to advance. Such knowledge is crucial for improved management of acid-peptic disorders.
Topics: Chloride Channels; Gastric Acid; Gastric Mucosa; Gastrins; Gastrointestinal Microbiome; Histamine; Humans; Neurosecretory Systems; Potassium Channels; Proton Pump Inhibitors; Somatostatin
PubMed: 27607343
DOI: 10.1097/MOG.0000000000000308 -
Advances in Experimental Medicine and... 2019Colic is a common and distressing functional gastrointestinal disorder during infancy. It is a behavioral phenomenon in infants aged 1-4 months involving prolonged... (Review)
Review
Colic is a common and distressing functional gastrointestinal disorder during infancy. It is a behavioral phenomenon in infants aged 1-4 months involving prolonged inconsolable crying and agitated status with multifactorial etiology. Colic can be considered as a benign, self-limited process because the baby normally grows and feeds even with transient irritable mood. Nevertheless, infantile colic is a common difficulty causing anxiety during parenthood and a recurrent reason for them to seek medical help, especially if it is the first child. The causes of colic can be classified as non-gastrointestinal or gastrointestinal. The former includes altered feeding techniques, modified child-parent relationship, immaturity of central nervous system, behavioral etiology, and maternal smoking or nicotine replacement therapy. Instead, the latter involves inadequate production of lactase enzyme, cow's milk protein intolerance, alteration of intestinal microbiota, gastrointestinal immaturity, or inflammation which causes intestinal hyperperistalsis due to increase in serotonin secretion and motilin receptor expression.Probiotics may play a crucial part in the manipulation of the microbiota. Probiotic administration is likely to maintain intestinal homeostasis through the modulation of permeability and peristalsis, influencing the gut-brain axis and inhibiting hypersensitivity. This is a decisive field in the development of preventive and therapeutic strategies for infantile colic. However, further studies are needed for each specific formulation in order to better characterize pharmacodynamic and pharmacokinetic properties and to evaluate their application as a possible preventive strategy if administered early during infancy against the later development of pain-related FGIDs.
Topics: Colic; Food Intolerance; Gastrointestinal Microbiome; Humans; Infant; Probiotics
PubMed: 30656551
DOI: 10.1007/5584_2018_315 -
Current Opinion in Endocrinology,... Apr 2022In this review, we evaluate recent findings related to the association between gastrointestinal hormones and regulation of gastric emptying. (Review)
Review
PURPOSE OF REVIEW
In this review, we evaluate recent findings related to the association between gastrointestinal hormones and regulation of gastric emptying.
RECENT FINDINGS
Motilin and ghrelin, which act during fasting, promote gastric motility, whereas most of the hormones secreted after a meal inhibit gastric motility. Serotonin has different progastric or antigastric motility effects depending on the receptor subtype. Serotonin receptor agonists have been used clinically to treat dyspepsia symptoms but other hormone receptor agonists or antagonists are still under development. Glucagon-like peptide 1 agonists, which have gastric motility and appetite-suppressing effects are used as a treatment for obesity and diabetes.
SUMMARY
Gastrointestinal hormones play an important role in the regulation of gastric motility. Various drugs have been developed to treat delayed gastric emptying by targeting gastrointestinal hormones or their receptors but few have been commercialized.
Topics: Fasting; Gastric Emptying; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Hormones; Gastrointestinal Motility; Ghrelin; Humans; Motilin
PubMed: 35081068
DOI: 10.1097/MED.0000000000000707 -
Handbook of Experimental Pharmacology 2017Ghrelin and motilin are released from gastrointestinal endocrine cells during hunger, to act through G protein-coupled receptors that have closely related amino acid... (Review)
Review
Ghrelin and motilin are released from gastrointestinal endocrine cells during hunger, to act through G protein-coupled receptors that have closely related amino acid sequences. The actions of ghrelin are more complex than motilin because ghrelin also exists outside the GI tract, it is processed to des-acyl ghrelin which has activity, ghrelin can exist in truncated forms and retain activity, the ghrelin receptor can have constitutive activity and is subject to biased agonism and finally additional ghrelin-like and des-acyl ghrelin receptors are proposed. Both ghrelin and motilin can stimulate gastric emptying, acting via different pathways, perhaps influenced by biased agonism at the receptors, but research is revealing additional pathways of activity. For example, it is becoming apparent that reduction of nausea may be a key therapeutic target for ghrelin receptor agonists and perhaps for compounds that modulate the constitutive activity of the ghrelin receptor. Reduction of nausea may be the mechanism through which gastroparesis symptoms are reduced. Intriguingly, a potential ability of motilin to influence nausea is also becoming apparent. Ghrelin interacts with digestive function through its effects on appetite, and ghrelin antagonists may have a place in treating Prader-Willi syndrome. Unlike motilin, ghrelin receptor agonists also have the potential to treat constipation by acting at the lumbosacral defecation centres. In conclusion, agonists of both ghrelin and motilin receptors hold potential as treatments for specific subsets of digestive system disorders.
Topics: Animals; Appetite Regulation; Enteric Nervous System; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Motility; Gastrointestinal Tract; Ghrelin; Humans; Motilin; Neural Pathways; Receptors, Gastrointestinal Hormone; Receptors, Ghrelin; Receptors, Neuropeptide; Signal Transduction
PubMed: 28035532
DOI: 10.1007/164_2016_104 -
Peptides Feb 2023Motilin is a gastrointestinal hormone secreted by the duodenum. This peptide regulates a characteristic gastrointestinal contraction pattern, called the migrating motor... (Review)
Review
Motilin is a gastrointestinal hormone secreted by the duodenum. This peptide regulates a characteristic gastrointestinal contraction pattern, called the migrating motor complex, during the fasting state. Motilin also affects the pressure of the lower esophageal sphincter, gastric motility and gastric accommodation in the gastrointestinal tract. Furthermore, motilin induces bile discharge into the duodenum by promoting gallbladder contraction, pepsin secretion in the stomach, pancreatic juice and insulin secretion from the pancreas. In recent years, it has been shown that motilin is associated with appetite, and clinical applications are expected for diseases affected by food intake, e.g. obesity, by regulating motilin levels. Gastric acid and bile are the two major physiological regulators for motilin release. Caloric foods have varying effects on motilin levels, depending on their composition. Among non-caloric foods, bitter substances reduce motilin levels and are therefore expected to have an appetite-suppressing effect. Various motilin receptor agonists and antagonists have been developed but have yet to reach clinical use.
Topics: Motilin; Gastrointestinal Motility; Stomach; Gastrointestinal Hormones; Myoelectric Complex, Migrating; Duodenum
PubMed: 36436612
DOI: 10.1016/j.peptides.2022.170905 -
Internal Medicine Journal Aug 2020Gastroparesis is a syndrome characterised by delayed gastric emptying in the absence of mechanical obstruction. Symptoms can include early satiety, abdominal pain,... (Review)
Review
Gastroparesis is a syndrome characterised by delayed gastric emptying in the absence of mechanical obstruction. Symptoms can include early satiety, abdominal pain, bloating, vomiting and regurgitation which cause significant morbidity in addition to nutritional deficits. There is a higher prevalence in diabetics and females, but the incidence in the Australian population has not been well studied. Management of gastroparesis involves investigating and correcting nutritional deficits, optimising glycaemic control and improving gastrointestinal motility. Symptom control in gastroparesis can be challenging. Nutritional deficits should be addressed initially through dietary modification. Enteral feeding is a second-line option when oral intake is insufficient. Home parenteral nutrition is rarely used, and only accessible through specialised clinics in the outpatient setting. Prokinetic medication classes that have been used include dopamine receptor antagonists, motilin receptor agonists, 5-HT receptor agonists and ghrelin receptor agonists. Anti-emetic agents are often used for symptom control. Interventional treatments include gastric electrical stimulation, gastric per-oral endoscopic myotomy, feeding jejunostomy and gastrostomy/jejunstomy for gastric venting and enteral feeding. In this article we propose a framework to manage gastroparesis in Australia based on current evidence and available therapies.
Topics: Antiemetics; Australia; Female; Gastric Emptying; Gastroparesis; Gastrostomy; Humans; Vomiting
PubMed: 31314176
DOI: 10.1111/imj.14438 -
Neurogastroenterology and Motility Apr 2019There have been many recent advances in the understanding of various aspects of the physiology of gastric motility and gastric emptying. Earlier studies had discovered... (Review)
Review
There have been many recent advances in the understanding of various aspects of the physiology of gastric motility and gastric emptying. Earlier studies had discovered the remarkable ability of the stomach to regulate the timing and rate of emptying of ingested food constituents and the underlying motor activity. Recent studies have shown that two parallel neural circuits, the gastric inhibitory vagal motor circuit (GIVMC) and the gastric excitatory vagal motor circuit (GEVMC), mediate gastric inhibition and excitation and therefore the rate of gastric emptying. The GIVMC includes preganglionic cholinergic neurons in the DMV and the postganglionic inhibitory neurons in the myenteric plexus that act by releasing nitric oxide, ATP, and peptide VIP. The GEVMC includes distinct gastric excitatory preganglionic cholinergic neurons in the DMV and postganglionic excitatory cholinergic neurons in the myenteric plexus. Smooth muscle is the final target of these circuits. The role of the intramuscular interstitial cells of Cajal in neuromuscular transmission remains debatable. The two motor circuits are differentially regulated by different sets of neurons in the NTS and vagal afferents. In the digestive period, many hormones including cholecystokinin and GLP-1 inhibit gastric emptying via the GIVMC, and in the inter-digestive period, hormones ghrelin and motilin hasten gastric emptying by stimulating the GEVMC. The GIVMC and GEVMC are also connected to anorexigenic and orexigenic neural pathways, respectively. Identification of the control circuits of gastric emptying may provide better delineation of the pathophysiology of abnormal gastric emptying and its relationship to satiety signals and food intake.
Topics: Animals; Enteric Nervous System; Gastric Emptying; Gastrointestinal Motility; Ghrelin; Humans; Motilin; Neurons
PubMed: 30740834
DOI: 10.1111/nmo.13546 -
Nature Reviews. Endocrinology Apr 2019After the discovery of motilin in 1972, motilin and the motilin receptor were studied intensely for their role in the control of gastrointestinal motility and as targets... (Review)
Review
After the discovery of motilin in 1972, motilin and the motilin receptor were studied intensely for their role in the control of gastrointestinal motility and as targets for treating hypomotility disorders. The genetic revolution - with the use of knockout models - sparked novel insights into the role of multiple peptides but contributed to a decline in interest in motilin, as this peptide and its receptor exist only as pseudogenes in rodents. The past 5 years have seen a major surge in interest in motilin, as a series of studies have shown its relevance in the control of hunger and regulation of food intake in humans in both health and disease. Luminal stimuli, such as bitter tastants, have been identified as modulators of motilin release, with effects on hunger and food intake. The current state of knowledge and potential implications for therapy are summarized in this Review.
Topics: Animals; Dogs; Eating; Gastric Emptying; Gastrointestinal Motility; Humans; Hunger; Mice; Motilin; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Sensitivity and Specificity
PubMed: 30675023
DOI: 10.1038/s41574-019-0155-0