Seven transmembrane G protein-coupled receptor repertoire of gastric ghrelin cells
Maja S. Engelstoft,Won-Mee Park,Ichiro Sakata,Line Vildbrad Kristensen,Anna Sofie Husted,Sherri Osborne-Lawrence,Paul K Piper,Angela K. Walker,Maria Pedersen,Mark K. Nøhr,Jie Pan,Christopher Joseph Sinz,Paul E. Carrington,Taro E. Akiyama,Robert M. Jones,Cong Tang,Kashan Ahmed,Stefan Offermanns,Kristoffer L. Egerod,Jeffrey M. Zigman,Thue W. Schwartz +20 more
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TLDR
Highly expressed and enriched 7TM receptors and associated Gα subunits constitute a major part of the molecular machinery directly mediating neuronal and endocrine stimulation versus metabolite and somatostatin inhibition of ghrelin secretion including a series of novel receptor targets not previously identified on the gh Relin cell.Abstract:
The molecular mechanisms regulating secretion of the orexigenic-glucoregulatory hormone ghrelin remain unclear. Based on qPCR analysis of FACS-purified gastric ghrelin cells, highly expressed and enriched 7TM receptors were comprehensively identified and functionally characterized using in vitro, ex vivo and in vivo methods. Five Gαs-coupled receptors efficiently stimulated ghrelin secretion: as expected the β1-adrenergic, the GIP and the secretin receptors but surprisingly also the composite receptor for the sensory neuropeptide CGRP and the melanocortin 4 receptor. A number of Gαi/o-coupled receptors inhibited ghrelin secretion including somatostatin receptors SSTR1, SSTR2 and SSTR3 and unexpectedly the highly enriched lactate receptor, GPR81. Three other metabolite receptors known to be both Gαi/o- and Gαq/11-coupled all inhibited ghrelin secretion through a pertussis toxin-sensitive Gαi/o pathway: FFAR2 (short chain fatty acid receptor; GPR43), FFAR4 (long chain fatty acid receptor; GPR120) and CasR (calcium sensing receptor). In addition to the common Gα subunits three non-common Gαi/o subunits were highly enriched in ghrelin cells: GαoA, GαoB and Gαz. Inhibition of Gαi/o signaling via ghrelin cell-selective pertussis toxin expression markedly enhanced circulating ghrelin. These 7TM receptors and associated Gα subunits constitute a major part of the molecular machinery directly mediating neuronal and endocrine stimulation versus metabolite and somatostatin inhibition of ghrelin secretion including a series of novel receptor targets not previously identified on the ghrelin cell.read more
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Enteroendocrine Cells: Chemosensors in the Intestinal Epithelium.
Fiona M. Gribble,Frank Reimann +1 more
TL;DR: Characterizing the roles and functions of different enteroendocrine cells is an essential step in understanding the physiology, pathophysiology, and therapeutics of the gut-brain-pancreas axis.
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Free Fatty Acid Receptors in Health and Disease.
TL;DR: Recent reports on the key physiological functions of the FFAR-mediated signaling transduction pathways in the regulation of metabolism and immune responses are discussed and future research opportunities for developing therapeutics for metabolic and immune disorders are revealed.
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Ghrelin, CCK, GLP-1, and PYY(3-36): Secretory Controls and Physiological Roles in Eating and Glycemia in Health, Obesity, and After RYGB.
Robert E. Steinert,Christine Feinle-Bisset,Lori Asarian,Michael Horowitz,Christoph Beglinger,Nori Geary +5 more
TL;DR: Gastric emptying, the detection of specific digestive products by small intestinal enteroendocrine cells, and synergistic interactions among different GI loci all contribute to the secretion of ghrelin, CCK, GLP-1, and PYY(3-36).
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GPCR-Mediated Signaling of Metabolites
TL;DR: Different metabolite GPCRs act as efficient pro- and anti-inflammatory regulators of key immune cells, and signaling metabolites may thus function as important drivers of the low-grade inflammation associated with insulin resistance and obesity.
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Function and mechanisms of enteroendocrine cells and gut hormones in metabolism.
Fiona M. Gribble,Frank Reimann +1 more
TL;DR: Modulating the release of the endogenous stores of GLP1 and other gut hormones is thought to be a promising strategy to mimic bariatric surgery with its multifaceted beneficial effects on food intake, body weight and blood glucose levels.
References
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Ghrelin is a growth-hormone-releasing acylated peptide from stomach.
TL;DR: The occurrence of ghrelin in both rat and human indicates that GH release from the pituitary may be regulated not only by hypothalamic GHRH, but also by ghrelIn, a peptide specifically releases GH both in vivo and in vitro.
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Ghrelin induces adiposity in rodents.
TL;DR: It is proposed that ghrelin, in addition to its role in regulating GH secretion, signals the hypothalamus when an increase in metabolic efficiency is necessary, suggesting an involvement in regulation of energy balance.
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A Preprandial Rise in Plasma Ghrelin Levels Suggests a Role in Meal Initiation in Humans
David E. Cummings,Jonathan Q. Purnell,R. Scott Frayo,Karin Schmidova,Brent E. Wisse,David S. Weigle +5 more
TL;DR: The hypothesis that ghrelin plays a physiological role in meal initiation in humans is supported by the clear preprandials rise and postprandial fall in plasma ghrelIn levels.
Journal ArticleDOI
The gut microbiota — masters of host development and physiology
TL;DR: The gut microbiota has a beneficial role during normal homeostasis, modulating the host's immune system as well as influencing host development and physiology, including organ development and morphogenesis, and host metabolism.
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Ghrelin, a novel growth hormone-releasing acylated peptide, is synthesized in a distinct endocrine cell type in the gastrointestinal tracts of rats and humans.
Yukari Date,Masayasu Kojima,Hiroshi Hosoda,Akira Sawaguchi,Muhtashan S. Mondal,Tatsuo Suganuma,Shigeru Matsukura,Kenji Kangawa,Masamitsu Nakazato +8 more
TL;DR: Ghrelin probably functions not only in the control of GH secretion, but also in the regulation of diverse processes of the digestive system, and its findings provide clues to additional physiological functions of this novel gastrointestinal hormone.
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