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Cong Tang, Stefan Offermanns
The short-chain fatty acid receptors FFA2 (GPR43) and FFA3 (GPR41) are activated by acetate, propionate, and butyrate. These ligands are produced by bacteria in the gut. In addition, the body itself can in particular produce acetate, and acetate plasma levels have been shown to be increased, e.g., in diabetic patients or during periods of starvation. FFA2 and FFA3 are both expressed by enteroendocrine cells and pancreatic β-cells. In addition, FFA2 is found on immune cells and adipocytes, whereas FFA3 is expressed by some peripheral neurons...
October 19, 2016: Handbook of Experimental Pharmacology
Linda J Fothergill, Brid Callaghan, Leni R Rivera, TinaMarie Lieu, Daniel P Poole, Hyun-Jung Cho, David M Bravo, John B Furness
TRPA1 is a ligand-activated cation channel found in the intestine and other tissues. Components of food that stimulate TRPA1 receptors (phytonutrients) include allyl isothiocyanate, cinnamaldehyde and linalool, but these may also act at other receptors. Cells lining the intestinal mucosa are immunoreactive for TRPA1 and Trpa1 mRNA occurs in mucosal extracts, suggesting that the TRPA1 receptor is the target for these agonists. However, in situ hybridisation reveals Trpa1 expression in 5-HT containing enteroendocrine cells, not enterocytes...
October 10, 2016: Nutrients
Alan J Simmons, Cherié R Scurrah, Eliot T McKinley, Charles A Herring, Jonathan M Irish, M Kay Washington, Robert J Coffey, Ken S Lau
Cellular heterogeneity poses a substantial challenge to understanding tissue-level phenotypes and confounds conventional bulk analyses. To analyze signaling at the single-cell level in human tissues, we applied mass cytometry using cytometry time of flight to formalin-fixed, paraffin-embedded (FFPE) normal and diseased intestinal specimens. This technique, called FFPE-DISSECT (disaggregation for intracellular signaling in single epithelial cells from tissue), is a single-cell approach to characterizing signaling states in embedded tissue samples...
October 11, 2016: Science Signaling
Jiangtian Chen, Wencke Reiher, Christiane Hermann-Luibl, Azza Sellami, Paola Cognigni, Shu Kondo, Charlotte Helfrich-Förster, Jan A Veenstra, Christian Wegener
Feeding and sleep are fundamental behaviours with significant interconnections and cross-modulations. The circadian system and peptidergic signals are important components of this modulation, but still little is known about the mechanisms and networks by which they interact to regulate feeding and sleep. We show that specific thermogenetic activation of peptidergic Allatostatin A (AstA)-expressing PLP neurons and enteroendocrine cells reduces feeding and promotes sleep in the fruit fly Drosophila. The effects of AstA cell activation are mediated by AstA peptides with receptors homolog to galanin receptors subserving similar and apparently conserved functions in vertebrates...
September 2016: PLoS Genetics
Wenda Wu, Hui-Ren Zhou, Steven J Bursian, Jane E Link, James J Pestka
The common foodborne mycotoxin deoxynivalenol (DON, vomitoxin) can negatively impact animal and human health by causing food refusal and vomiting. Gut enteroendocrine cells (EECs) secrete hormones that mediate DON's anorectic and emetic effects. In prior work utilizing a cloned EEC model, our laboratory discovered that DON-induced activation of calcium-sensing receptor (CaSR), a G-coupled protein receptor (GPCR), and transient receptor ankyrin-1 (TRPA1), a transient receptor potential (TRP) channel, drives Ca(2+)-mediated hormone secretion...
September 25, 2016: Toxicological Sciences: An Official Journal of the Society of Toxicology
Sara Baldassano, Antonella Amato, Flavia Mulè
Glucagon like peptide-2 (GLP-2) is a gastrointestinal hormone released from enteroendocrine L-type cells together with glucagon like peptide-1 in response to dietary nutrients. GLP-2 acts through a specific receptor, the GLP-2 receptor, mainly located in the gut and in the brain. Classically, GLP-2 is considered a trophic hormone involved in the maintenance of intestinal epithelial morphology and function. This role has been targeted for therapies promoting repair and adaptive growth of the intestinal mucosa...
September 21, 2016: Peptides
Chris de Graaf, Dan Donnelly, Denise Wootten, Jesper Lau, Patrick M Sexton, Laurence J Miller, Jung-Mo Ahn, Jiayu Liao, Madeleine M Fletcher, Dehua Yang, Alastair J H Brown, Caihong Zhou, Jiejie Deng, Ming-Wei Wang
The glucagon-like peptide (GLP)-1 receptor (GLP-1R) is a class B G protein-coupled receptor (GPCR) that mediates the action of GLP-1, a peptide hormone secreted from three major tissues in humans, enteroendocrine L cells in the distal intestine, α cells in the pancreas, and the central nervous system, which exerts important actions useful in the management of type 2 diabetes mellitus and obesity, including glucose homeostasis and regulation of gastric motility and food intake. Peptidic analogs of GLP-1 have been successfully developed with enhanced bioavailability and pharmacological activity...
October 2016: Pharmacological Reviews
Thomas U Greiner, Fredrik Bäckhed
BACKGROUND: The gut microbiota is associated with several of metabolic diseases, including obesity and type 2 diabetes and affects host physiology through distinct mechanisms. The microbiota produces a vast array of metabolites that signal to host cells in the intestine as well as in more distal organs. SCOPE OF REVIEW: Enteroendocrine cells acts as 'chemo sensors' of the intestinal milieu by expressing a large number of receptors, which respond to different metabolites and nutrients, and signal to host by a wide variety of hormones...
September 2016: Molecular Metabolism
Michael Camilleri, Ibironke Oduyebo, Houssam Halawi
Several chemical and molecular factors are reported to be altered and to have a potentially significant role in irritable bowel syndrome (IBS), particularly in IBS with diarrhea (IBS-D). These include bile acids, short chain fatty acids, mucosal barrier proteins, mast cell products such as histamine, proteases and tryptase, enteroendocrine cell products, and mucosal mRNAs, proteins and micro-RNAs. This article reviews the current knowledge and unanswered questions in the pathobiology of the chemical and molecular factors in IBS...
September 8, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Helen M Cox
Enteroendocrine cells (EECs) contain different combinations of hormones, which are released following stimulation of nutrient receptors that are selectively expressed by these cells. This chemosensation varies according to the intestinal area and species of interest, and responses to meals are rapidly modified following bariatric surgery. Such surgically-induced gastrointestinal (GI) changes highlight considerable enteroplasticity, however our understanding of even the acute physiological control and consequences of neuroendocrine peptide release is still under-developed...
September 3, 2016: Current Opinion in Pharmacology
Tarek Mazzawi, Magdy El-Salhy
The enteroendocrine cells of the ileum are stimulated by the luminal contents to release specific hormones that regulate its functions. The density of ileal enteroendocrine cells is abnormal in patients with irritable bowel syndrome (IBS), and the majority of patients with IBS associate their symptoms to the consumption of certain foodstuffs. The present study investigated the effect of dietary guidance on the enteroendocrine cells of the ileum in 11 patients with IBS. A total of 10 control subjects were also included...
September 2016: Experimental and Therapeutic Medicine
Helle A Hassing, Suzan Fares, Olav Larsen, Hamideh Pad, Maria Hauge, Robert M Jones, Thue W Schwartz, Harald S Hansen, Mette M Rosenkilde
GPR119 is a Gαs-coupled lipid-sensor in the gut, where it mediates release of incretin hormones from the enteroendocrine cells and in pancreatic α-cells, where it releases insulin. Naturally occurring lipids such as monoacylglycerols (MAGs) and N-acylethanolamines (NAEs), like oleoylethanolamide (OEA), activate GPR119, and multiple synthetic ligands have been described. Here, we extend the GPR119 signaling profile to Gαq and Gαi in addition to β-arrestin recruitment and the downstream transcription factors CRE (cAMP response element), SRE (serum response element) and NFAT (nuclear factor of activated T cells)...
November 1, 2016: Biochemical Pharmacology
Steven K Malin, Sangeeta R Kashyap
Bariatric surgery is a gastrointestinal procedure that has emerged as the most effective treatment for weight loss. Roux-en-Y gastric bypass and sleeve gastrectomy are the main procedures currently performed. However, the benefits of bariatric surgery extend beyond weight loss. In fact, improvements in β-cell function occur before clinically meaningful weight loss and contribute to type 2 diabetes mellitus (T2D) remission. Herein, we discuss evidence supporting the efficacy of bariatric surgery for weight loss and improved insulin secretion in patients with and without T2D...
July 2016: Surgery for Obesity and related Diseases: Official Journal of the American Society for Bariatric Surgery
Christopher M McLaughlin, Sandrina Lampis, Milena Mechkarska, Laurent Coquet, Thierry Jouenne, Jay D King, Maria Luisa Mangoni, Miodrag L Lukic, Mariano A Scorciapino, J Michael Conlon
Four host-defense peptides belonging to the tigerinin family (tigerinin-1O: RICTPIPFPMCY; tigerinin-2O: RTCIPIPLVMC; tigerinin-3O: RICTAIPLPMCL; and tigerinin-4O: RTCIPIPPVCF) were isolated from skin secretions of the African crowned bullfrog Hoplobatrachus occipitalis. In aqueous solution at pH 4.8, the cyclic domain of tigerinin-2O adopts a rigid amphipathic conformation that incorporates a flexible N-terminal tail. The tigerinins lacked antimicrobial (MIC > 100 μM) and hemolytic (LC50 > 500 μM) activities but, at a concentration of 20 μg/mL, significantly (P < 0...
September 23, 2016: Journal of Natural Products
Rodolphe Dusaulcy, Sandra Handgraaf, Svetlana Skarupelova, Florian Visentin, Christian Vesin, Mounia Heddad-Masson, Frank Reimann, Fiona Gribble, Jacques Philippe, Yvan Gosmain
Glucose homeostasis depends on the coordinated secretion of glucagon, insulin, and Glucagon-like peptide (GLP)-1 by pancreas and intestine. Obesity, which is associated with an increased risk of developing insulin resistance and type 2 diabetes, affects the function of these organs. Here, we investigate the functional and molecular adaptations of proglucagon-producing cells in obese mice to better define their involvement in type 2 diabetes development. We used GLU-Venus transgenic male mice specifically expressing Venus fluorochrome in proglucagon-producing cells...
October 2016: Endocrinology
José Antonio Hernández-Trejo, Dimelza Lisett Suárez-Pérez, Itzel Zenidel Gutiérrez-Martínez, Omar E Fernandez-Vargas, Carolina Serrano, Aurora Antonia Candelario Martínez, Marco Antonio Meraz Ríos, Alí Francisco Citalán Madrid, Marcela Hernández Ruíz, Elba Reyes-Maldonado, Ricard Valle-Ríos, Jacobo Feintuch-Unger, Michael Schnoor, Nicolás Villegas-Sepúlveda, Oscar Medina Contreras, Porfirio Nava Domínguez
The gastrointestinal (GI) tract is the largest hormone-producing organ in the body due to a specialized cell population called enteroendocrine cells (EECs). The number of EECs increases in the mucosa of inflammatory bowel disease (IBD) patients; however, the mechanisms responsible for these changes remain unknown. Here, we show that the proinflammatory cytokines IFNγ and TNFα or DSS induced colitis increased the number of EECs producing Chromogranin A (CgA) in the colonic mucosa of C57BL/6J mice. CgA-positive cells were non-proliferating cells enriched with inactive PTEN and autophagy markers...
August 18, 2016: Biochemical Journal
Thâmarah A Lima, Kenner M Fernandes, Ana Patrícia S Oliveira, Leonardo P Dornelles, Gustavo F Martins, Thiago H Napoleão, Patrícia M G Paiva
BACKGROUND: Myracrodruon urundeuva is a hardwood tree whose bark, heartwood, and leaf contain lectins (MuBL, MuHL and MuLL, respectively) with termiticidal activity against Nasutitermes corniger. In this work, the effects of these lectins on the midgut of N. corniger workers were evaluated. RESULTS: The insects were supplied with an artificial diet containing the lectins at their respective LC50 (previously determined). Forty-eight hours after the treatment, the midguts were dissected and fixed for histopathology analyses...
August 16, 2016: Pest Management Science
Nadin Al Shukor, Rozenn Ravallec, John Van Camp, Katleen Raes, Guy Smagghe
Animal experiments showed that flavonoids might have the potential for an anti-obesity effect by reducing weight and food intake. However, the exact mechanisms that could be involved in these proposed effects are still under investigation. The complex process of food intake is partially regulated by gastrointestinal hormones. Cholecystokinin (CCK) is the best known gastrointestinal hormone to induce satiety signal that plays a key role in food intake regulation. It is released from the endocrine cells (I cell) in response to the ingestion of nutrients into the small intestine...
September 2016: Fitoterapia
Yueyue Yu, Lei Lu, Jun Sun, Elaine O Petrof, Erika C Claud
Development of the infant small intestine is influenced by bacterial colonization. To promote establishment of optimal microbial communities in preterm infants, knowledge of the beneficial functions of the early gut microbiota on intestinal development is needed. The purpose of this study was to investigate the impact of early preterm infant microbiota on host gut development using a gnotobiotic mouse model. Histological assessment of intestinal development was performed. The differentiation of four epithelial cell lineages (enterocytes, goblet cells, Paneth cells, enteroendocrine cells) and tight junction (TJ) formation was examined...
September 1, 2016: American Journal of Physiology. Gastrointestinal and Liver Physiology
Kyle N Kunze, Erin C Hanlon, Vivek N Prachand, Matthew J Brady
Thirteen percent of the world's population suffers from obesity and 39% from being overweight, which correlates with an increase in numerous secondary metabolic complications, such as Type 2 diabetes mellitus. Bariatric surgery is the most effective treatment for severe obesity and results in significant weight loss and the amelioration of obesity-related comorbidities through changes in enteroendocrine activity, caloric intake, and alterations in gut microbiota composition. The circadian system has recently been found to be a critical regulatory component in the control of metabolism and, thus, may potentially play an important role in inappropriate weight gain...
September 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
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