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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 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 -
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 -
Minerva Pediatrics Oct 2021Functional constipation is an important clinical problem among chidren all over the world. Its main cause is not completely understood. Motilin is a gastrointestinal...
BACKGROUND
Functional constipation is an important clinical problem among chidren all over the world. Its main cause is not completely understood. Motilin is a gastrointestinal hormone that increases intestinal motility. In this study, we aimed to investigate the serum motilin levels and its relationship with stool consistency and motilin gene polymorphisms in constipated children.
METHODS
In this study we investigated 91 constipated patients (mean age 6.84±3.55 years) and 100 healthy controls (mean age 7.78±4.25 years). Serum motilin levels were assessed by sandwich enzyme-linked immunosorbent assay. rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) mutations were evaluated for motilin gene polymorphisms.
RESULTS
Serum motilin levels were significantly lower in constipated children than healthy controls (6.20±7.86 vs. 11.54±17.89 pg/mL, respectively, P=0.008). Serum motilin levels were significantly correlated with Bristol stool scale rate (r=0.193, P=0.011) in whole study group, but in the constipation group there was no significant correlation (r=-0.072, P=0.528). There were no differences in terms of presence or distribution of the polymorphisms of rs2281820 (c.44 C>T) and rs2281818 (c.66 C>T) in both groups. There was not a significant difference between different polymorphism groups regarding serum motilin concentrations in whole study group and also in both of the study groups.
CONCLUSIONS
This study indicated for the first time that serum motilin levels decreased in constipated children. Further studies are needed to clarify whether motilin or motilin gene polymorphisms has a role in pathogenesis of functional constipation.
Topics: Child; Child, Preschool; Constipation; Gastrointestinal Motility; Humans; Motilin; Polymorphism, Genetic
PubMed: 27706119
DOI: 10.23736/S2724-5276.16.04369-X -
Expert Review of Gastroenterology &... Feb 2020: Motilin was first alluded to nearly a century ago. But it remains a rather abstruse peptide, in the shadow of its younger but more lucid 'cousin' ghrelin.: The review... (Review)
Review
: Motilin was first alluded to nearly a century ago. But it remains a rather abstruse peptide, in the shadow of its younger but more lucid 'cousin' ghrelin.: The review aimed to bring to the fore multifarious aspects of motilin research with a view to aiding prioritization of future studies on this gastrointestinal peptide.: Growing evidence indicates that rodents (mice, rats, guinea pigs) do not have functional motilin system and, hence, studies in these species are likely to have a minimal translational impact. Both the active peptide and motilin receptor were initially localized to the upper gastrointestinal tract only but more recently - also to the brain (in both humans and other mammals with functional motilin system). Motilin is now indisputably implicated in interdigestive contractile activity of the gastrointestinal tract (in particular, gastric phase III of the migrating motor complex). Beyond this role, evidence is building that there is a cross-talk between motilin system and the brain-pancreas axis, suggesting that motilin exerts not only contractile but also orexigenic and insulin secretagogue actions.
Topics: Animals; Brain; Gastrointestinal Motility; Gastrointestinal Tract; Ghrelin; Humans; Hunger; Insulin; Motilin; Myoelectric Complex, Migrating; Pancreas; Receptor Cross-Talk; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide; Signal Transduction
PubMed: 31996050
DOI: 10.1080/17474124.2020.1718492 -
Frontiers in Endocrinology 2021Motilin, produced in endocrine cells in the mucosa of the upper intestine, is an important regulator of gastrointestinal (GI) motility and mediates the phase III of... (Review)
Review
Motilin, produced in endocrine cells in the mucosa of the upper intestine, is an important regulator of gastrointestinal (GI) motility and mediates the phase III of interdigestive migrating motor complex (MMC) in the stomach of humans, dogs and house musk shrews through the specific motilin receptor (MLN-R). Motilin-induced MMC contributes to the maintenance of normal GI functions and transmits a hunger signal from the stomach to the brain. Motilin has been identified in various mammals, but the physiological roles of motilin in regulating GI motility in these mammals are well not understood due to inconsistencies between studies conducted on different species using a range of experimental conditions. Motilin orthologs have been identified in non-mammalian vertebrates, and the sequence of avian motilin is relatively close to that of mammals, but reptile, amphibian and fish motilins show distinctive different sequences. The MLN-R has also been identified in mammals and non-mammalian vertebrates, and can be divided into two main groups: mammal/bird/reptile/amphibian clade and fish clade. Almost 50 years have passed since discovery of motilin, here we reviewed the structure, distribution, receptor and the GI motility regulatory function of motilin in vertebrates from fish to mammals.
Topics: Animals; Gastrointestinal Motility; Humans; Motilin; Muscle Contraction; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide
PubMed: 34497583
DOI: 10.3389/fendo.2021.700884 -
Science Advances Mar 2023Motilin is an endogenous peptide hormone almost exclusively expressed in the human gastrointestinal (GI) tract. It activates the motilin receptor (MTLR), a class A G...
Motilin is an endogenous peptide hormone almost exclusively expressed in the human gastrointestinal (GI) tract. It activates the motilin receptor (MTLR), a class A G protein-coupled receptor (GPCR), and stimulates GI motility. To our knowledge, MTLR is the first GPCR reported to be activated by macrolide antibiotics, such as erythromycin. It has attracted extensive attention as a potential drug target for GI disorders. We report two structures of G-coupled human MTLR bound to motilin and erythromycin. Our structures reveal the recognition mechanism of both ligands and explain the specificity of motilin and ghrelin, a related gut peptide hormone, for their respective receptors. These structures also provide the basis for understanding the different recognition modes of erythromycin by MTLR and ribosome. These findings provide a framework for understanding the physiological regulation of MTLR and guiding drug design targeting MTLR for the treatment of GI motility disorders.
Topics: Humans; Motilin; Erythromycin; Receptors, Gastrointestinal Hormone; Receptors, Neuropeptide
PubMed: 36921049
DOI: 10.1126/sciadv.ade9020 -
International Journal of Medical... 2022Grape seed is an important natural bioactive product with various health benefits. Interstitial cells of Cajal (ICCs) are pacemaker cells in the gastrointestinal (GI)...
Grape seed is an important natural bioactive product with various health benefits. Interstitial cells of Cajal (ICCs) are pacemaker cells in the gastrointestinal (GI) tract. The present study investigated the effects of grape seed powder (GSP) on ICC properties and GI motility. GSP depolarized the pacemaker potentials of ICCs in a dose‑dependent manner. Y25130 or SB269970 slightly inhibited GSP‑induced effects. However, Y25130 and SB269970 together completely blocked GSP-induced effects. In the presence of inhibitors of protein kinase C, protein kinase A, or mitogen-activated protein kinase, GSP‑induced ICC depolarization was inhibited. GSP increased the intestinal transit rate in normal mice and in mice with acetic acid-induced GI motility disorder. In addition, the levels of motilin and substance P were elevated after GSP dosing. These results demonstrate that GSP can regulate GI motility, and therefore, it is a potential therapeutic agent for treating GI motility disorders.
Topics: Animals; Gastrointestinal Motility; Intestine, Small; Membrane Potentials; Mice; Patch-Clamp Techniques; Powders; Seeds; Vitis
PubMed: 35693751
DOI: 10.7150/ijms.72529