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Enteroendocrine

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https://www.readbyqxmd.com/read/28523577/ffa3-activation-stimulates-duodenal-bicarbonate-secretion-and-prevents-nsaid-induced-enteropathy-via-the-glp-2-pathway-in-rats
#1
Hyder Said, Yasutada Akiba, Kazuyuki Narimatsu, Koji Maruta, Ayaka Kuri, Ken-Ichi Iwamoto, Atsukazu Kuwahara, Jonathan D Kaunitz
BACKGROUND: Therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) is associated with enteropathy in humans and experimental animals, a cause of considerable morbidity. Unlike foregut NSAID-associated mucosal lesions, most treatments for this condition are of little efficacy. We propose that the endogenously released intestinotrophic hormone glucagon-like peptide-2 (GLP-2) prevents the development of NSAID-induced enteropathy. Since the short-chain fatty acid receptor FFA3 is expressed on enteroendocrine L cells and on enteric nerves in the gastrointestinal tract, we further hypothesized that activation of FFA3 on L cells protects the mucosa from injury via GLP-2 release with enhanced duodenal HCO3(-) secretion...
May 18, 2017: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/28523111/discovery-of-orally-efficacious-tetrahydrobenzimidazoles-as-tgr5-agonists-for-type-2-diabetes
#2
Xuqing Zhang, Mark Wall, Zhihua Sui, Jack Kauffman, Cuifen Hou, Cailin Chen, Fuyong Du, Thomas Kirchner, Yin Liang, Dana L Johnson, William V Murray, Keith Demarest
We have discovered a novel series of tetrahydrobenzimidazoles 3 as TGR5 agonists. Initial structure-activity relationship studies with an assay that measured cAMP levels in murine enteroendocrine cells (STC-1 cells) led to the discovery of potent agonists with submicromolar EC50 values for mTGR5. Subsequent optimization through methylation of the 7-position of the core tetrahydrobenzimidazole ring resulted in the identification of potent agonists for both mTGR5 and hTGR5 (human enteroendocrine NCI-H716 cells)...
May 11, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28510488/distinct-effects-of-growth-hormone-and-glutamine-on-activation-of-intestinal-stem-cells
#3
Yun Chen, Sheng-Hong Tseng, Chao-Ling Yao, Chuan Li, Ya-Hui Tsai
BACKGROUND: For patients with short bowel syndrome under parenteral nutrition support, growth hormone (GH) and glutamine (GLN) have been found to help the growth of intestinal mucosa. In this research, we studied the effects of GH and GLN on intestinal stem cells (ISCs). METHODS: The in vitro and in vivo effects of GH and/or GLN on ISCs were evaluated by observing the ability of ISCs to form organoids in a Matrigel culture system. The expression levels of stemness and differentiation markers in ISCs and organoids were assessed using quantitative real-time polymerase chain reaction, immunofluorescence assay, and immunohistochemistry staining...
May 1, 2017: JPEN. Journal of Parenteral and Enteral Nutrition
https://www.readbyqxmd.com/read/28501979/endocrine-cells-producing-peptide-hormones-in-the-intestine-of-nile-tilapia-distribution-and-effects-of-feeding-and-fasting-on-the-cell-density
#4
Raquel Tatiane Pereira, Thaiza Rodrigues de Freitas, Izabela Regina Cardoso de Oliveira, Leandro Santos Costa, Fabricio Andrés Vigliano, Priscila Vieira Rosa
Endocrine cells (ECs) act as a luminal surveillance system responding to either the presence or absence of food in the gut through the secretion of peptide hormones. The aim of this study was to analyze the effects of feeding and fasting on the EC peptide-specific distribution along the intestine of Nile tilapia. We assessed the density of ECs producing gastrin (GAS), cholecystokinin-8 (CCK-8), neuropeptide Y (NPY), and calcitonin gene-related peptide (CGRP) in nine segments of the intestine using immunohistochemistry...
May 13, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28485065/heterogeneity-of-enterochromaffin-cells-within-the-gastrointestinal-tract
#5
REVIEW
S Diwakarla, L J Fothergill, J Fakhry, B Callaghan, J B Furness
Enterochromaffin cells were the first endocrine cells of the gastrointestinal tract to be chemically distinguished, almost 150 years ago. It is now known that the chromaffin reaction of these cells was due to their content of the reactive aromatic amine, 5-hydroxytryptamine (5-HT, also known as serotonin). They have commonly been thought to be a special class of gut endocrine cells (enteroendocrine cells) that are distinct from the enteroendocrine cells that contain peptide hormones. The study by Martin et al...
June 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
https://www.readbyqxmd.com/read/28484425/protein-digestion-derived-peptides-and-the-peripheral-regulation-of-food-intake
#6
REVIEW
Juliette Caron, Dorothée Domenger, Pascal Dhulster, Rozenn Ravallec, Benoit Cudennec
The gut plays a central role in energy homeostasis. Food intake regulation strongly relies on the gut-brain axis, and numerous studies have pointed out the significant role played by gut hormones released from enteroendocrine cells. It is well known that digestive products of dietary protein possess a high satiating effect compared to carbohydrates and fat. Nevertheless, the processes occurring in the gut during protein digestion involved in the short-term regulation of food intake are still not totally unraveled...
2017: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/28483523/effect-of-essential-amino-acids-on-enteroids-methionine-deprivation-suppresses-proliferation-and-affects-differentiation-in-enteroid-stem-cells
#7
Yuki Saito, Ken Iwatsuki, Hikaru Hanyu, Natsuki Maruyama, Eitaro Aihara, Miki Tadaishi, Makoto Shimizu, Kazuo Kobayashi-Hattori
We investigated the effects of essential amino acids on intestinal stem cell proliferation and differentiation using murine small intestinal organoids (enteroids) from the jejunum. By selectively removing individual essential amino acids from culture medium, we found that 24 h of methionine (Met) deprivation markedly suppressed cell proliferation in enteroids. This effect was rescued when enteroids cultured in Met deprivation media for 12 h were transferred to complete medium, suggesting that Met plays an important role in enteroid cell proliferation...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28475172/keratins-regulate-colonic-epithelial-cell-differentiation-through-the-notch1-signalling-pathway
#8
Iris A K Lähdeniemi, Julia O Misiorek, Christian J M Antila, Sebastian K-J Landor, Carl-Gustaf A Stenvall, Lina E Fortelius, Linda K Bergström, Cecilia Sahlgren, Diana M Toivola
Keratins (K) are intermediate filament proteins important in stress protection and mechanical support of epithelial tissues. K8, K18 and K19 are the main colonic keratins, and K8-knockout (K8(-/-)) mice display a keratin dose-dependent hyperproliferation of colonic crypts and a colitis-phenotype. However, the impact of the loss of K8 on intestinal cell differentiation has so far been unknown. Here we show that K8 regulates Notch1 signalling activity and differentiation in the epithelium of the large intestine...
May 5, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28448057/mixed-primary-cultures-of-murine-small-intestine-intended-for-the-study-of-gut-hormone-secretion-and-live-cell-imaging-of-enteroendocrine-cells
#9
Arianna Psichas, Gwen Tolhurst, Cheryl A Brighton, Fiona M Gribble, Frank Reimann
The gut is the largest endocrine organ of the body, with hormone-secreting enteroendocrine cells located along the length of the gastrointestinal epithelium. Despite their physiological importance, enteroendocrine cells represent only a small fraction of the epithelial cell population and in the past, their characterization has presented a considerable challenge resulting in a reliance on cell line models. Here, we provide a detailed protocol for the isolation and culture of mixed murine small intestinal cells...
April 20, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28431319/response-of-plasma-glucagon-like-peptide-2-to-feeding-pattern-and-intraruminal-administration-of-volatile-fatty-acids-in-sheep
#10
M Elsabagh, Y Inabu, T Obitsu, T Sugino
Glucagon-like peptide-2 (GLP-2), a gut peptide secreted by enteroendocrine L cells, has recently been identified as a key regulator of intestinal growth and absorptive function in ruminants. However, reports on GLP-2 secretion are few, and more information regarding its secretion dynamics is needed. In this study, two experiments were conducted to elucidate the daily rhythm of GLP-2 secretion in response to feeding regimen and to investigate the effect of volatile fatty acids (VFA) on GLP-2 release in sheep...
March 11, 2017: Domestic Animal Endocrinology
https://www.readbyqxmd.com/read/28430903/co-storage-of-enteroendocrine-hormones-evaluated-at-the-cell-and-subcellular-levels-in-male-mice
#11
Linda J Fothergill, Brid Callaghan, Billie Hunne, David M Bravo, John B Furness
Recent studies reveal complex patterns of hormone co-expression within enteroendocrine cells (EEC), contrary to the traditional view that gut hormones are expressed individually in EEC. Moreover, different hormones have been found in separate subcellular vesicles. However, detailed analysis of relative expression of multiple hormones has not been made. Subcellular studies have been confined to peptide hormones, and have not included the indolamine, 5-HT, or the neuroendocrine protein, chromogranin A (CgA). In the present work, co-expression of 5-HT, CgA, secretin, CCK, ghrelin, and GLP-1 in mouse duodenum was quantified at a cellular and subcellular level by semi-automated cell counting and quantitative vesicle measurements...
April 18, 2017: Endocrinology
https://www.readbyqxmd.com/read/28429513/distribution-and-hormonal-characterization-of-primary-murine-l-cells-throughout-the-gastrointestinal-tract
#12
Kazuyo Suzuki, Kanako Iwasaki, Yuki Murata, Norio Harada, Shunsuke Yamane, Akihiro Hamasaki, Kimitaka Shibue, Erina Joo, Akiko Sankoda, Yuta Fujiwara, Yoshitaka Hayashi, Nobuya Inagaki
AIMS/INTRODUCTION: Glucagon-like peptide-1 (GLP-1) secreted from enteroendocrine L-cells is an incretin that potentiates insulin secretion and is already applied in therapies for type 2 diabetes. However, detailed examination of L-cells throughout the gastrointestinal (GI) tract remains unclear, because of difficulties in purifying scattered L-cells from other cells. In the present study, we identified characteristics of L-cells of the upper small intestine (UI), the lower small intestine (LI) and the colon using glucagon (Gcg)-green fluorescent protein (GFP)-expressing mice that express GFP driven by the proglucagon promoter...
April 20, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28428611/transcription-factor-antagonism-controls-enteroendocrine-cell-specification-from-intestinal-stem-cells
#13
Yumei Li, Zhimin Pang, Huanwei Huang, Chenhui Wang, Tao Cai, Rongwen Xi
The balanced maintenance and differentiation of local stem cells is required for Homeostatic renewal of tissues. In the Drosophila midgut, the transcription factor Escargot (Esg) maintains undifferentiated states in intestinal stem cells, whereas the transcription factors Scute (Sc) and Prospero (Pros) promote enteroendocrine cell specification. However, the mechanism through which Esg and Sc/Pros coordinately regulate stem cell differentiation is unknown. Here, by combining chromatin immunoprecipitation analysis with genetic studies, we show that both Esg and Sc bind to a common promoter region of pros...
April 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28414465/topical-intestinal-aminoimidazole-agonists-of-g-protein-coupled-bile-acid-receptor-1-promote-glucagon-like-peptide-1-secretion-and-improve-glucose-tolerance
#14
Manuel Lasalle, Vanessa Hoguet, Nathalie Hennuyer, Florence Leroux, Catherine Piveteau, Loïc Belloy, Sophie Lestavel, Emmanuelle Vallez, Emilie Dorchies, Isabelle Duplan, Emmanuel Sevin, Maxime Culot, Fabien Gosselet, Rajaa Boulahjar, Adrien Herledan, Bart Staels, Benoit Deprez, Anne Tailleux, Julie Charton
The role of the G-protein-coupled bile acid receptor TGR5 in various organs, tissues, and cell types, specifically in intestinal endocrine L-cells and brown adipose tissue, has made it a promising therapeutical target in several diseases, especially type-2 diabetes and metabolic syndrome. However, recent studies have shown deleterious on-target effects of systemic TGR5 agonists. To avoid these systemic effects while stimulating glucagon-like peptide-1 (GLP-1) secreting enteroendocrine L-cells, we have designed TGR5 agonists with low intestinal permeability...
May 5, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28413860/distribution-and-characterisation-of-cck-containing-enteroendocrine-cells-of-the-mouse-small-and-large-intestine
#15
Josiane Fakhry, Joyce Wang, Patricia Martins, Linda J Fothergill, Billie Hunne, Pierre Prieur, Arthur Shulkes, Jens F Rehfeld, Brid Callaghan, John B Furness
There is general consensus that enteroendocrine cells, EEC, containing the enteric hormone cholecystokinin (CCK) are confined to the small intestine and predominate in the duodenum and jejunum. Contrary to this, EEC that express the gene for CCK have been isolated from the large intestine of the mouse and there is evidence for EEC that contain CCK-like immunoreactivity in the mouse colon. However, the human and rat colons do not contain CCK cells. In the current study, we use immunohistochemistry to investigate CCK peptide presence in endocrine cells, PCR to identify cck transcripts and chromatography to identify CCK peptide forms in the mouse small and large intestine...
April 17, 2017: Cell and Tissue Research
https://www.readbyqxmd.com/read/28380372/gpcr-mediated-signaling-of-metabolites
#16
REVIEW
Anna Sofie Husted, Mette Trauelsen, Olga Rudenko, Siv A Hjorth, Thue W Schwartz
In addition to their bioenergetic intracellular function, several classical metabolites act as extracellular signaling molecules activating cell-surface G-protein-coupled receptors (GPCRs), similar to hormones and neurotransmitters. "Signaling metabolites" generated from nutrients or by gut microbiota target primarily enteroendocrine, neuronal, and immune cells in the lamina propria of the gut mucosa and the liver and, through these tissues, the rest of the body. In contrast, metabolites from the intermediary metabolism act mainly as metabolic stress-induced autocrine and paracrine signals in adipose tissue, the liver, and the endocrine pancreas...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28359759/a-vesicle-trafficking-protein-%C3%AE-snap-regulates-paneth-cell-differentiation-in%C3%A2-vivo
#17
Susana Lechuga, Nayden G Naydenov, Alex Feygin, Antonio J Jimenez, Andrei I Ivanov
A soluble N-ethylmaleimide-sensitive factor-attachment protein alpha (αSNAP) is a multifunctional scaffolding protein that regulates intracellular vesicle trafficking and signaling. In cultured intestinal epithelial cells, αSNAP has been shown to be essential for cell survival, motility, and adhesion; however, its physiologic functions in the intestinal mucosa remain unknown. In the present study, we used a mouse with a spontaneous hydrocephalus with hop gait (hyh) mutation of αSNAP to examine the roles of this trafficking protein in regulating intestinal epithelial homeostasis in vivo...
May 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28336548/nutrient-sensing-by-absorptive-and-secretory-progenies-of-small-intestinal-stem-cells
#18
Kunihiro Kishida, Sarah C Pearce, Shiyan Yu, Nan Gao, Ronaldo P Ferraris
Nutrient sensing triggers responses by the gut-brain axis modulating hormone release, feeding behavior and metabolism that become dysregulated in metabolic syndrome and some cancers. Except for absorptive enterocytes and secretory enteroendocrine cells, the ability of many intestinal cell types to sense nutrients is still unknown, hence we hypothesized that progenitor stem cells (ISC) possess nutrient sensing ability inherited by progenies during differentiation. We directed via modulators of Wnt and Notch signaling, differentiation of precursor mouse intestinal crypts into specialized organoids each containing ISC, enterocyte, goblet or Paneth cells at relative proportions much higher than in situ as determined by mRNA expression and immunocytochemistry of cell type biomarkers...
March 23, 2017: American Journal of Physiology. Gastrointestinal and Liver Physiology
https://www.readbyqxmd.com/read/28325479/the-role-of-pancreatic-preproglucagon-in-glucose-homeostasis-in-mice
#19
Adam P Chambers, Joyce E Sorrell, April Haller, Karen Roelofs, Chelsea R Hutch, Ki-Suk Kim, Ruth Gutierrez-Aguilar, Bailing Li, Daniel J Drucker, David A D'Alessio, Randy J Seeley, Darleen A Sandoval
Glucagon-like peptide 1 (GLP-1) is necessary for normal gluco-regulation, and it has been widely presumed that this function reflects the actions of GLP-1 released from enteroendocrine L cells. To test the relative importance of intestinal versus pancreatic sources of GLP-1 for physiological regulation of glucose, we administered a GLP-1R antagonist, exendin-[9-39] (Ex9), to mice with tissue-specific reactivation of the preproglucagon gene (Gcg). Ex9 impaired glucose tolerance in wild-type mice but had no impact on Gcg-null or GLP-1R KO mice, suggesting that Ex9 is a true and specific GLP-1R antagonist...
April 4, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28324023/long-chain-free-fatty-acid-receptor-gpr120-mediates-oil-induced-gip-secretion-through-cck-in-male-mice
#20
Akiko Sankoda, Norio Harada, Kanako Iwasaki, Shunsuke Yamane, Yuki Murata, Kimitaka Shibue, Yotsapon Thewjitcharoen, Kazuyo Suzuki, Takanari Harada, Yoshinori Kanemaru, Satoko Shimazu-Kuwahara, Akira Hirasawa, Nobuya Inagaki
Free fatty acid receptors GPR120 and GPR40 are involved in the secretion of gut hormones. GPR120 and GPR40 are expressed in enteroendocrine K-cells and their activation induces the secretion of the incretin glucose-dependent insulinotropic polypeptide (GIP). However, the role of these receptors in fat-induced GIP secretion in vivo and the associated mechanisms are unclear. In this study, we investigated corn oil-induced GIP secretion in GPR120-knockout (GPR120-/-) and GPR40-knockout (GPR40-/-) mice. Oil-induced GIP secretion was reduced by 50% and 80% in GPR120-/- and GPR40-/- mice compared to that in wild-type (WT) mice, respectively...
March 15, 2017: Endocrinology
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