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Current Opinion in Endocrinology,... Feb 2019This review examines the hormonal regulation of gastric emptying, a topic of increasing relevance, given the fact that medications that are analogs of some of these... (Review)
Review
PURPOSE OF REVIEW
This review examines the hormonal regulation of gastric emptying, a topic of increasing relevance, given the fact that medications that are analogs of some of these hormones or act as agonists at the hormonal receptors, are used in clinical practice for optimizing metabolic control in the treatment of type 2 diabetes and in obesity.
RECENT FINDINGS
The major effects on gastric emptying result from actions of incretins, particularly gastric inhibitory polypeptide, glucagon-like peptide-1, and peptide tyrosine-tyrosine, the duodenal and pancreatic hormones, motilin, glucagon, and amylin, and the gastric orexigenic hormones, ghrelin and motilin. All of these hormones delay gastric emptying, except for ghrelin and motilin which accelerate gastric emptying. These effects on gastric emptying parallel the effects of the hormones on satiation (by those retarding emptying) and increase appetite by those that accelerate emptying. Indeed, in addition to the effects of these hormones on hypothalamic appetite centers and glycemic control, there is evidence that some of their biological effects are mediated through actions on the stomach, particularly with the glucagon-like peptide-1 analogs or agonists used in treating obesity.
SUMMARY
Effects of gastrointestinal hormones on gastric emptying are increasingly recognized as important mediators of satiation and postprandial glycemic control.
Topics: Appetite; Diabetes Mellitus, Type 2; Gastric Emptying; Gastrointestinal Hormones; Humans; Obesity; Satiation
PubMed: 30418188
DOI: 10.1097/MED.0000000000000448 -
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 -
Nature Reviews. Gastroenterology &... Jan 2016The gastrointestinal tract is the major source of the related hormones ghrelin and motilin, which act on structurally similar G protein-coupled receptors. Nevertheless,... (Review)
Review
The gastrointestinal tract is the major source of the related hormones ghrelin and motilin, which act on structurally similar G protein-coupled receptors. Nevertheless, selective receptor agonists are available. The primary roles of endogenous ghrelin and motilin in the digestive system are to increase appetite or hedonic eating (ghrelin) and initiate phase III of gastric migrating myoelectric complexes (motilin). Ghrelin and motilin also both inhibit nausea. In clinical trials, the motilin receptor agonist camicinal increased gastric emptying, but at lower doses reduced gastroparesis symptoms and improved appetite. Ghrelin receptor agonists have been trialled for the treatment of diabetic gastroparesis because of their ability to increase gastric emptying, but with mixed results; however, relamorelin, a ghrelin agonist, reduced nausea and vomiting in patients with this disorder. Treatment of postoperative ileus with a ghrelin receptor agonist proved unsuccessful. Centrally penetrant ghrelin receptor agonists stimulate defecation in animals and humans, although ghrelin itself does not seem to control colorectal function. Thus, the most promising uses of motilin receptor agonists are the treatment of gastroparesis or conditions with slow gastric emptying, and ghrelin receptor agonists hold potential for the reduction of nausea and vomiting, and the treatment of constipation. Therapeutic, gastrointestinal roles for receptor antagonists or inverse agonists have not been identified.
Topics: Appetite; Constipation; Gastric Emptying; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Motility; Ghrelin; Humans; Hunger; Motilin; Nausea; Receptors, Gastrointestinal Hormone; Receptors, Ghrelin; Receptors, Neuropeptide; Signal Transduction
PubMed: 26392067
DOI: 10.1038/nrgastro.2015.163 -
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 -
Veterinary Journal (London, England :... Apr 2015Displacement of the abomasum (DA) is a common inherited condition in Holstein cows. This article reviews the genetics of DA including risk factors, genetic parameters... (Review)
Review
Displacement of the abomasum (DA) is a common inherited condition in Holstein cows. This article reviews the genetics of DA including risk factors, genetic parameters and molecular genetic results. Breeds other than Holsteins affected by DA include Guernseys, Jerseys, Brown Swiss, Ayrshires and Simmental-Red Holsteins. In most DA cases, left displacements of the abomasum (LDA) are seen. Lactation incidence rates are higher for DA in first lactation Holsteins compared to later lactations. For Holstein cows, heritability estimates for DA are between 0.03 and 0.53. Genetic correlation estimates among DA and milk production traits range from positive to negative. Genome-wide significant genomic regions associated with LDA are located on bovine chromosomes (BTA) 1, 3, 11, 20 and 23. Motilin-associated single nucleotide polymorphisms on BTA23 exhibit a functional relationship with LDA. Pathways for deposition of calcium, insulin-dependent diabetes mellitus and synaptic transmission are significantly related to LDA in Holsteins. Deciphering the DA-associated genomic regions and genes may be an important step in the quest to understand the underlying disease-causing mechanisms and in unravelling mutations with a causal relationship to DA.
Topics: Abomasum; Animals; Cattle; Cattle Diseases; Genetic Predisposition to Disease; Genome-Wide Association Study; Genomics; Stomach Diseases
PubMed: 25840863
DOI: 10.1016/j.tvjl.2015.02.013 -
Clinical Therapeutics Jun 2018This review provides an update on the investigations and treatment options for gastroparesis. (Review)
Review
PURPOSE
This review provides an update on the investigations and treatment options for gastroparesis.
METHODS
A comprehensive literature search of Medline, PubMed, Embase and OVID was conducted which included all systematic reviews and research articles that focused on the diagnosis, investigations and management diabetic gastroparesis.
FINDINGS
Dietary modifications and pharmacologic treatment with prokinetics to increase gastric motility form the mainstay of treatment. However, the use of prokinetics is limited by adverse effects and serious adverse effects, leaving metoclopramide as the only drug approved by the US Food and Drug Administration for the treatment of gastroparesis. Newer therapies, including motilin receptor agonists, ghrelin receptor agonists, and neurokinin receptor antagonists, are currently being investigated. Transpyloric stenting, gastric electrical stimulation, and gastric per-oral endoscopic myotomy provide mechanical options for intervention, and surgical interventions in severe intractable gastroparesis include laparoscopic pyloroplasty or gastrectomy.
IMPLICATIONS
Advances to better understand the pathophysiology and management of diabetic gastroparesis have been limited, especially with discordance between symptoms and severity of delay in gastric emptying. Established treatment options are limited; however, recent pharmacologic and surgical interventions show promise.
Topics: Animals; Diabetic Neuropathies; Gastroparesis; Humans
PubMed: 29748143
DOI: 10.1016/j.clinthera.2018.04.012 -
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 -
Expert Opinion on Emerging Drugs Jun 2015Functional dyspepsia (FD) is a relatively common gastrointestinal clinical condition that remains poorly understood. Controversies remain regarding the definition,... (Review)
Review
INTRODUCTION
Functional dyspepsia (FD) is a relatively common gastrointestinal clinical condition that remains poorly understood. Controversies remain regarding the definition, pathophysiology and optimum treatment. The current treatment of FD is limited and no established regimen is available.
AREAS COVERED
Recent advances have improved our understanding of the pathophysiology of the disease and have led to the development of newer tailored therapies. Novel agents such as the motilin receptor agonist camicinal and the muscarinic M1 and M2 receptor antagonist acotiamide appear promising; however, the need for a safe and efficacious treatment remains largely unmet. This review describes the currently available management options for FD and critically evaluates emerging therapies.
EXPERT OPINION
The optimal treatment for FD is yet to be determined. A proton pump inhibitor or a prokinetic agent constitutes primary treatment. Helicobacter pylori testing and eradication is recommended. Based on currently available data, acotiamide appears promising, particularly in postprandial distress syndrome. Further large-scale multicentered trials are required to define the duration of treatment and the side-effect profile.
Topics: Benzamides; Drug Design; Dyspepsia; Gastrointestinal Agents; Helicobacter Infections; Helicobacter pylori; Humans; Postprandial Period; Proton Pump Inhibitors; Thiazoles
PubMed: 25645940
DOI: 10.1517/14728214.2015.1009827