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https://www.readbyqxmd.com/read/28325479/the-role-of-pancreatic-preproglucagon-in-glucose-homeostasis-in-mice
#1
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...
March 9, 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
#2
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
https://www.readbyqxmd.com/read/28323941/the-diverse-metabolic-roles-of-peripheral-serotonin
#3
Alyce M Martin, Richard L Young, Lex Leong, Geraint B Rogers, Nick J Spencer, Claire F Jessup, Damien J Keating
Serotonin (5-hydroxytryptamine, 5-HT) is a multi-functional bioamine with important signaling roles in a range of physiological pathways. Almost all the 5-HT in our body is synthesized in specialized enteroendocrine cells within the gastrointestinal (GI) mucosa called enterochromaffin (EC) cells. These cells provide all our circulating 5-HT. While we have long appreciated the important roles of 5-HT within the gut including the modulation of GI motility, there is recently emerging evidence of the physiological and clinical significance of gut-derived 5-HT outside of the gut...
March 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/28320893/regional-differences-in-nutrient-induced-secretion-of-gut-serotonin
#4
Alyce M Martin, Amanda L Lumsden, Richard L Young, Claire F Jessup, Nick J Spencer, Damien J Keating
Enterochromaffin (EC) cells located in the gastrointestinal (GI) tract provide the vast majority of serotonin (5-HT) in the body and constitute half of all enteroendocrine cells. EC cells respond to an array of stimuli, including various ingested nutrients. Ensuing 5-HT release from these cells plays a diverse role in regulating gut motility as well as other important responses to nutrient ingestion such as glucose absorption and fluid balance. Recent data also highlight the role of peripheral 5-HT in various pathways related to metabolic control...
March 2017: Physiological Reports
https://www.readbyqxmd.com/read/28317734/aroma-compound-diacetyl-suppresses-glucagon-like-peptide-1-production-and-secretion-in-stc-1-cells
#5
Triona McCarthy, Christine Bruen, Fiona O'Halloran, Harriet Schellekens, Kieran Kilcawley, John F Cryan, Linda Giblin
Diacetyl is a volatile flavour compound that has a characteristic buttery aroma and is widely used in the flavour industry. The aroma of a food plays an important role in food palatability and thus intake. This study investigates the effect of diacetyl on the satiety hormone, glucagon-like peptide (GLP-1), using the enteroendocrine cell line, STC-1. Diacetyl decreased proglucagon mRNA and total GLP-1 from glucose stimulated STC-1 cells. This dampening effect on GLP-1 appears to be mediated by increasing intracellular cAMP levels, increasing synthesis of the G protein coupled receptor, GPR120, and its recruitment to the cell surface...
August 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28286046/rudimentary-expression-of-ryamide-in-drosophila-melanogaster-relative-to-other-drosophila-species-points-to-a-functional-decline-of-this-neuropeptide-gene
#6
Jan A Veenstra, Hela Khammassi
RYamides are arthropod neuropeptides with unknown function. In 2011 two RYamides were isolated from D. melanogaster as the ligands for the G-protein coupled receptor CG5811. The D. melanogaster gene encoding these neuropeptides is highly unusual, as there are four RYamide encoding exons in the current genome assembly, but an exon encoding a signal peptide is absent. Comparing the D. melanogaster gene structure with those from other species, including D. virilis, suggests that the gene is degenerating. RNAseq data from 1634 short sequence read archives at NCBI containing more than 34 billion spots yielded numerous individual spots that correspond to the RYamide encoding exons, of which a large number include the intron-exon boundary at the start of this exon...
March 7, 2017: Insect Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28275690/intestinal-epithelial-specific-mtorc1-activation-enhances-intestinal-adaptation-after-small-bowel-resection
#7
Lauren Barron, Raphael C Sun, Bola Aladegbami, Christopher R Erwin, Brad W Warner, Jun Guo
BACKGROUND & AIMS: Intestinal adaptation is a compensatory response to the massive loss of small intestine after surgical resection. We investigated the role of intestinal epithelial cell-specific mammalian target of rapamycin complex 1 (i-mTORC1) in intestinal adaptation after massive small bowel resection (SBR). METHODS: We performed 50% proximal SBR on mice to study adaptation. To manipulate i-mTORC1 activity, Villin-Cre(ER) transgenic mice were crossed with tuberous sclerosis complex (TSC)1(flox/flox) or Raptor(flox/flox) mice to inducibly activate or inactivate i-mTORC1 activity with tamoxifen...
March 2017: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28271031/enteroendocrine-derived-glucagon-like-peptide-2-controls-intestinal-amino-acid-transport
#8
Jennifer Lee, Jacqueline Koehler, Bernardo Yusta, Jasmine Bahrami, Dianne Matthews, Mahroukh Rafii, Paul B Pencharz, Daniel J Drucker
OBJECTIVE: Glucagon-like peptide-2 (GLP-2) is co-secreted with GLP-1 from gut endocrine cells, and both peptides act as growth factors to expand the surface area of the mucosal epithelium. Notably, GLP-2 also enhances glucose and lipid transport in enterocytes; however, its actions on control of amino acid (AA) transport remain unclear. Here we examined the mechanisms linking gain and loss of GLP-2 receptor (GLP-2R) signaling to control of intestinal amino acid absorption in mice. METHODS: Absorption, transport, and clearance of essential AAs, specifically lysine, were measured in vivo by Liquid Chromatography triple quadrupole Mass Spectrometry (LC-MS/MS) and ex vivo with Ussing chambers using intestinal preparations from Glp2r(+/+) and Glp2r(-/-) mice...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28271030/high-fidelity-glucagon-creer-mouse-line-generated-by-crispr-cas9-assisted-gene-targeting
#9
Amanda M Ackermann, Jia Zhang, Aryel Heller, Anna Briker, Klaus H Kaestner
OBJECTIVE: α-cells are the second most prominent cell type in pancreatic islets and are responsible for producing glucagon to increase plasma glucose levels in times of fasting. α-cell dysfunction and inappropriate glucagon secretion occur in both type 1 and type 2 diabetes. Thus, there is growing interest in studying both normal function and pathophysiology of α-cells. However, tools to target gene ablation or activation specifically of α-cells have been limited, compared to those available for β-cells...
March 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28259987/abnormal-differentiation-of-stem-cells-into-enteroendocrine-cells-in-rats-with-dss-induced-colitis
#10
Magdy El-Salhy, Kazuo Umezawa, Jan Gunnar Hatlebakk, Odd Helge Gilja
The present study aimed to determine whether there is an association between abnormalities in enteroendocrine cells in dextran sulfate sodium (DSS)‑induced colitis and the clonogenic and/or proliferative activities of stem cells. A total of 48 male Wistar rats were divided into four groups. Animals in the control group were provided with normal drinking water, whereas DSS colitis was induced in the remaining three groups. The rats with DSS‑induced colitis were randomized into the following three groups: i) DSS group, which received 0...
March 1, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28257936/signalling-in-the-gut-endocrine-axis
#11
REVIEW
Fiona M Gribble, Frank Reimann
Enteroendocrine cells are sensory cells located in the intestinal epithelium that produce a variety of hormonal regulators of gastrointestinal physiology, metabolism and food intake. They detect the absorption of a wide range of ingested nutrients via pathways that include transporter-mediated uptake, G-protein coupled receptors and ion channels. This review will describe mechanisms by which the L-cells that produce Glucagon Like Peptide-1 (GLP-1) respond to different components of ingested food, and the importance of these pathways not only for understanding physiology, but also for developing new treatments for type 2 diabetes and obesity...
February 28, 2017: Physiology & Behavior
https://www.readbyqxmd.com/read/28215313/low-molecular-fraction-of-wheat-protein-hydrolysate-stimulates-glucagon-like-peptide-1-secretion-in-an-enteroendocrine-l-cell-line-and-improves-glucose-tolerance-in-rats
#12
Masaki Kato, Takenori Nakanishi, Tsubasa Tani, Takanori Tsuda
The incretin hormone glucagon-like peptide-1 (GLP-1) is secreted by enteroendocrine L cells. Stimulating endogenous GLP-1 secretion by dietary factors is a promising strategy to increase GLP-1 action. Several studies have examined the specific physiological function of wheat protein hydrolysate. Some reports suggested that intake of wheat protein ameliorates hyperglycemia. We hypothesized that wheat protein hydrolysate reduces blood glucose concentration via stimulation of GLP-1 secretion. In this study, we investigated whether wheat protein hydrolysate stimulates GLP-1 secretion and its molecular mechanism in an enteroendocrine L cell line (GLUTag cells), and we examined the effect on glucose tolerance via stimulation of GLP-1 secretion followed by induction of insulin secretion in rats...
January 2017: Nutrition Research
https://www.readbyqxmd.com/read/28207290/fatty-acid-and-mineral-receptors-as-drug-targets-for-gastrointestinal-disorders
#13
Pawin Pongkorpsakol, Aekkacha Moonwiriyakit, Chatchai Muanprasat
Nutrient-sensing receptors, including fatty acid receptors (FFA1-FFA4), Ca(2+)-sensing receptors and Zn(2+)-sensing receptors, are involved in several biological processes. These receptors are abundantly expressed in the GI tract, where they have been shown to play crucial roles in regulating GI function. This review provides an overview of the GI functions of fatty acid and mineral receptors, including the regulation of gastric and enteroendocrine functions, GI motility, ion transport and cell growth. Recently, several lines of evidence have implicated these receptors as promising therapeutic targets for the treatment of GI disorders, for example, inflammatory bowel disease, colorectal cancer, metabolic syndrome and diarrheal diseases...
February 16, 2017: Future Medicinal Chemistry
https://www.readbyqxmd.com/read/28179449/the-gip-gipr-axis-is-functionally-linked-to-gh-secretion-increase-in-a-significant-proportion-of-gsp-somatotropinomas
#14
D Regazzo, M Losa, N M Albiger, M R Terreni, G Vazza, F Ceccato, E Emanuelli, L Denaro, C Scaroni, G Occhi
OBJECTIVE: Glucose-dependent insulinotropic polypeptide receptor (GIPR) overexpression has been recently described in a proportion of gsp(-) somatotropinomas and suggested to be associated with the paradoxical increase of GH (GH-PI) during an oral glucose load. DESIGN AND METHODS: This study was aimed at linking the GIP/GIPR pathway to GH secretion in 25 somatotropinomas-derived primary cultures and correlating molecular with clinical features in acromegalic patients...
May 2017: European Journal of Endocrinology
https://www.readbyqxmd.com/read/28178568/midgut-derived-activin-regulates-glucagon-like-action-in-the-fat-body-and-glycemic-control
#15
Wei Song, Daojun Cheng, Shangyu Hong, Benoit Sappe, Yanhui Hu, Neil Wei, Changqi Zhu, Michael B O'Connor, Pavlos Pissios, Norbert Perrimon
While high-caloric diet impairs insulin response to cause hyperglycemia, whether and how counter-regulatory hormones are modulated by high-caloric diet is largely unknown. We find that enhanced response of Drosophila adipokinetic hormone (AKH, the glucagon homolog) in the fat body is essential for hyperglycemia associated with a chronic high-sugar diet. We show that the activin type I receptor Baboon (Babo) autonomously increases AKH signaling without affecting insulin signaling in the fat body via, at least, increase of Akh receptor (AkhR) expression...
February 7, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28157495/map-k-ing-the-path-to-stem-cell-quiescence-and-the-elusive-enteroendocrine-cell
#16
Simon J Leedham
The existence and interaction of proliferating and quiescent intestinal stem cells have been debated since their discovery in the 1970s. In this issue of Cell Stem Cell, using murine intestinal organoids, Basak et al. (2017) induce stem cell quiescence by selective inhibition of EGF/MAPK signaling and define culture conditions that direct differentiation to the enteroendocrine lineage.
February 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28137842/enteroviruses-infect-human-enteroids-and-induce-antiviral-signaling-in-a-cell-lineage-specific-manner
#17
Coyne G Drummond, Alexa M Bolock, Congrong Ma, Cliff J Luke, Misty Good, Carolyn B Coyne
Enteroviruses are among the most common viral infectious agents of humans and are primarily transmitted by the fecal-oral route. However, the events associated with enterovirus infections of the human gastrointestinal tract remain largely unknown. Here, we used stem cell-derived enteroids from human small intestines to study enterovirus infections of the intestinal epithelium. We found that enteroids were susceptible to infection by diverse enteroviruses, including echovirus 11 (E11), coxsackievirus B (CVB), and enterovirus 71 (EV71), and that contrary to an immortalized intestinal cell line, enteroids induced antiviral and inflammatory signaling pathways in response to infection in a virus-specific manner...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28125357/mucosal-ecological-network-of-epithelium-and-immune-cells-for-gut-homeostasis-and-tissue-healing
#18
Yosuke Kurashima, Hiroshi Kiyono
The intestinal epithelial barrier includes columnar epithelial, Paneth, goblet, enteroendocrine, and tuft cells as well as other cell populations, all of which contribute properties essential for gastrointestinal homeostasis. The intestinal mucosa is covered by mucin, which contains antimicrobial peptides and secretory IgA and prevents luminal bacteria, fungi, and viruses from stimulating intestinal immune responses. Conversely, the transport of luminal microorganisms-mediated by M, dendritic, and goblet cells-into intestinal tissues facilitates the harmonization of active and quiescent mucosal immune responses...
January 11, 2017: Annual Review of Immunology
https://www.readbyqxmd.com/read/28123938/intestinal-invalidation-of-the-glucose-transporter-glut2-delays-tissue-distribution-of-glucose-and-reveals-an-unexpected-role-in-gut-homeostasis
#19
Charlotte C Schmitt, Thomas Aranias, Thomas Viel, Danielle Chateau, Maude Le Gall, Anne-Judith Waligora-Dupriet, Chloé Melchior, Ophélie Rouxel, Nathalie Kapel, Guillaume Gourcerol, Bertrand Tavitian, Agnès Lehuen, Edith Brot-Laroche, Armelle Leturque, Patricia Serradas, Alexandra Grosfeld
OBJECTIVE: Intestinal glucose absorption is orchestrated by specialized glucose transporters such as SGLT1 and GLUT2. However, the role of GLUT2 in the regulation of glucose absorption remains to be fully elucidated. METHODS: We wanted to evaluate the role of GLUT2 on glucose absorption and glucose homeostasis after intestinal-specific deletion of GLUT2 in mice (GLUT2(ΔIEC) mice). RESULTS: As anticipated, intestinal GLUT2 deletion provoked glucose malabsorption as visualized by the delay in the distribution of oral sugar in tissues...
January 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/28123937/fermentable-carbohydrate-stimulates-ffar2-dependent-colonic-pyy-cell-expansion%C3%A2-to%C3%A2-increase-satiety
#20
Lucy Brooks, Alexander Viardot, Anastasia Tsakmaki, Emilie Stolarczyk, Jane K Howard, Patrice D Cani, Amandine Everard, Michelle L Sleeth, Arianna Psichas, Jelena Anastasovskaj, Jimmy D Bell, Kim Bell-Anderson, Charles R Mackay, Mohammad A Ghatei, Stephen R Bloom, Gary Frost, Gavin A Bewick
OBJECTIVE: Dietary supplementation with fermentable carbohydrate protects against body weight gain. Fermentation by the resident gut microbiota produces short-chain fatty acids, which act at free fatty acid receptor 2 (FFAR2). Our aim was to test the hypothesis that FFAR2 is important in regulating the beneficial effects of fermentable carbohydrate on body weight and to understand the role of gut hormones PYY and GLP-1. METHODS: Wild-type or Ffar2(-/-) mice were fed an inulin supplemented or control diet...
January 2017: Molecular Metabolism
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