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Pyy and human

Magdy El-Salhy, Tarek Mazzawi, Kazuo Umezawa, Odd Helge Gilja
Patients with inflammatory bowel disease (IBD), as well as animal models of human IBD have abnormal enteroendocrine cells. The present study aimed to identify the possible mechanisms underlying these abnormalities. For this purpose, 40 male Wistar rats were divided into 4 groups as follows: the control group, the group with trinitrobenzene sulfonic acid (TNBS)-induced colitis with no treatment (TNBS group), the group with TNBS-induced colitis treated with 3-[(dodecylthiocarbonyl)-methyl]-glutarimide (DTCM-G; an activator protein-1 inhibitor) (DTCM-G group), and the group with TNBS-induced colitis treated with dehydroxymethylepoxyquinomicin (DHMEQ; a nuclear factor-κB inhibitor) treatment (DHMEQ group)...
October 24, 2016: International Journal of Molecular Medicine
John T McLaughlin, Shane McKie
Functional mapping of human brain activation has made it possible to understand how different nutrients in the gut impact on homeostatic and appetitive brain responses. Current data are limited, but nutrient-specific effects are observed, with differential responses to lipid and sugars. Responses are not a simple function of calorie intake. Gut hormones such as CCK, PYY, GLP-1 and ghrelin are implicated in these responses, but may not exert effects directly on the brain. Research is now addressing how these homeostatic signalling states (fasting/fed) interact with hedonic responses, such as those evoked by images of appealing food...
August 27, 2016: Current Opinion in Pharmacology
Dawood Khan, Srividya Vasu, R Charlotte Moffett, Nigel Irwin, Peter R Flatt
Recent evidence suggests that the classic gut peptide, Peptide YY (PYY), could play a fundamental role in endocrine pancreatic function. In the present study expression of PYY and its NPY receptors on mouse islets and immortalised rodent and human beta-cells was examined together with the effects of both major circulating forms of PYY, namely PYY(1-36) and PYY(3-36), on beta-cell function, murine islet adaptions to insulin deficiency/resistance, as well as direct effects on cultured beta-cell proliferation and apoptosis...
November 15, 2016: Molecular and Cellular Endocrinology
Ramona Pais, Juraj Rievaj, Pierre Larraufie, Fiona Gribble, Frank Reimann
Angiotensin II (Ang II) is the key hormone mediator of the renin angiotensin system, which regulates blood pressure and fluid and electrolyte balance in the body. Here we report that in the colonic epithelium, the Ang II type 1 receptor is highly and exclusively expressed in enteroendocrine L cells, which produce the gut hormones glucagon-like peptide-1 and peptide YY (PYY). Ang II stimulated glucagon-like peptide-1 and PYY release from primary cultures of mouse and human colon, which was antagonized by the specific Ang II type 1 receptor blocker candesartan...
October 2016: Endocrinology
Pierre Larraufie, Joël Doré, Nicolas Lapaque, Hervé M Blottière
The intestinal epithelium is an active barrier separating the host from its microbiota. It senses microbial compounds through expression of a wide range of receptors including the Toll-like receptors (TLRs). TLRs have been shown to regulate epithelium permeability or secretion of defensin by Paneth cells. However, the expression and function of TLRs in enteroendocrine L-cells, a specific subtype of intestinal cells secreting PYY and GLP-1, have not yet been assessed. PYY and GLP-1 are implicated in regulation of gut motility, food intake and insulin secretion, and are of great interest regarding obesity and type 2 diabetes...
July 12, 2016: Cellular Microbiology
Claire S Byrne, Edward S Chambers, Habeeb Alhabeeb, Navpreet Chhina, Douglas J Morrison, Tom Preston, Catriona Tedford, Julie Fitzpatrick, Cherag Irani, Albert Busza, Isabel Garcia-Perez, Sofia Fountana, Elaine Holmes, Anthony P Goldstone, Gary S Frost
BACKGROUND: Short-chain fatty acids (SCFAs), metabolites produced through the microbial fermentation of nondigestible dietary components, have key roles in energy homeostasis. Animal research suggests that colon-derived SCFAs modulate feeding behavior via central mechanisms. In humans, increased colonic production of the SCFA propionate acutely reduces energy intake. However, evidence of an effect of colonic propionate on the human brain or reward-based eating behavior is currently unavailable...
July 2016: American Journal of Clinical Nutrition
Jenny Tong, Harold W Davis, Amalia Gastaldelli, David D'Alessio
OBJECTIVES: Administration of ghrelin inhibits the acute insulin response to glucose and worsens IV glucose tolerance in healthy subjects. Evidence from preclinical studies suggests that ghrelin may have differential effects on glucose metabolism during fasting and feeding. Our objective was to test the effects of ghrelin on glucose and insulin responses during a meal tolerance test. DESIGN: Acyl ghrelin (0.26 and 2.0 μg/kg/h) or saline was infused in 13 healthy subjects on three separate occasions in randomized order...
June 2016: Journal of Clinical Endocrinology and Metabolism
Ramona Pais, Juraj Rievaj, Claire Meek, Gayan De Costa, Samanthie Jayamaha, R Todd Alexander, Frank Reimann, Fiona Gribble
KEY POINTS: Arginine vasopressin (AVP) stimulates the release of enteroendocrine L-cell derived hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) in vitro from mouse and human colons. This is mediated by the AVP receptor 1B, which is highly enriched in colonic L-cells and linked to the elevation of L-cell calcium and cAMP concentrations. By means of Ussing chambers, we show that AVP reduced colonic anion secretion, although this was blocked by a specific neuropeptide Y receptor Y1 receptor antagonist, suggesting that L-cell-released PYY acts locally on the epithelium to modulate fluid balance...
September 1, 2016: Journal of Physiology
Leona Wagner, Florian Kaestner, Raik Wolf, Harald Stiller, Ulrich Heiser, Susanne Manhart, Torsten Hoffmann, Jens-Ulrich Rahfeld, Hans-Ulrich Demuth, Matthias Rothermundt, Stephan von Hörsten
BACKGROUND: Dipeptidyl peptidase 4 (DPP4; EC; CD26) is a membrane-bound or shedded serine protease that hydrolyzes dipeptides from the N-terminus of peptides with either proline or alanine at the penultimate position. Substrates of DPP4 include several stress-related neuropeptides implicated in anxiety, depression and schizophrenia. A decline of DPP4-like activity has been reported in sera from depressed patient, but not fully characterized regarding DPP4-like enzymes, therapeutic interventions and protein...
June 2016: Neuropeptides
Rocco Latorre, Jennifer Huynh, Maurizio Mazzoni, Arpana Gupta, Elena Bonora, Paolo Clavenzani, Lin Chang, Emeran A Mayer, Roberto De Giorgio, Catia Sternini
Bitter taste receptors (T2Rs) are expressed in the mammalian gastrointestinal mucosa. In the mouse colon, T2R138 is localized to enteroendocrine cells and is upregulated by long-term high fat diet that induces obesity. The aims of this study were to test whether T2R38 expression is altered in overweight/obese (OW/OB) compared to normal weight (NW) subjects and characterize the cell types expressing T2R38, the human counterpart of mouse T2R138, in human colon. Colonic mucosal biopsies were obtained during colonoscopy from 35 healthy subjects (20 OW/OB and 15 NW) and processed for quantitative RT-PCR and immunohistochemistry using antibodies to T2R38, chromogranin A (CgA), glucagon like peptide-1 (GLP-1), cholecystokinin (CCK), or peptide YY (PYY)...
2016: PloS One
Susanne Raab, Haiyan Wang, Sabine Uhles, Nadine Cole, Ruben Alvarez-Sanchez, Basil Künnecke, Christoph Ullmer, Hugues Matile, Marc Bedoucha, Roger D Norcross, Nickki Ottaway-Parker, Diego Perez-Tilve, Karin Conde Knape, Matthias H Tschöp, Marius C Hoener, Sabine Sewing
OBJECTIVE: Type 2 diabetes and obesity are emerging pandemics in the 21st century creating worldwide urgency for the development of novel and safe therapies. We investigated trace amine-associated receptor 1 (TAAR1) as a novel target contributing to the control of glucose homeostasis and body weight. METHODS: We investigated the peripheral human tissue distribution of TAAR1 by immunohistochemistry and tested the effect of a small molecule TAAR1 agonist on insulin secretion in vitro using INS1E cells and human islets and on glucose tolerance in C57Bl6, and db/db mice...
January 2016: Molecular Metabolism
Signe Toräng, Kirstine Nyvold Bojsen-Møller, Maria Saur Svane, Bolette Hartmann, Mette Marie Rosenkilde, Sten Madsbad, Jens Juul Holst
Peptide YY (PYY) is a 36-amino-acid peptide released from enteroendocrine cells upon food intake. The NH2 terminally truncated metabolite, PYY3-36, exerts anorexic effects and has received considerable attention as a possible antiobesity drug target. The kinetics and degradation products of PYY metabolism are not well described. A related peptide, neuropeptide Y, may be degraded from the COOH terminus, and in vivo studies in pigs revealed significant COOH-terminal degradation of PYY. We therefore investigated PYY metabolism in vitro after incubation in human blood and plasma and in vivo after infusion of PYY1-36 and PYY3-36 in eight young, healthy men...
May 1, 2016: American Journal of Physiology. Regulatory, Integrative and Comparative Physiology
Joanna Luttikhold, Klaske van Norren, Herman Rijna, Nikki Buijs, Marjolein Ankersmit, Annemieke C Heijboer, Jeannette Gootjes, Bolette Hartmann, Jens J Holst, Luc Jc van Loon, Paul Am van Leeuwen
BACKGROUND: Jejunal feeding is preferred instead of gastric feeding in patients who are intolerant to gastric feeding or at risk of aspiration. However, the impact of gastric feeding compared with that of jejunal feeding on postprandial circulating plasma glucose and amino acid concentrations and the associated endocrine response in vivo in humans remains largely unexplored. OBJECTIVE: We compared the impact of administering enteral nutrition as either gastric feeding or jejunal feeding on endocrine responses in vivo in humans...
February 2016: American Journal of Clinical Nutrition
Alok Kumar Mishra, Vinay Dubey, Asit Ranjan Ghosh
Obesity is one of the major challenges for public health in 21st century, with 1.9 billion people being considered as overweight and 600 million as obese. There are certain diseases such as type 2 diabetes, hypertension, cardiovascular disease, and several forms of cancer which were found to be associated with obesity. Therefore, understanding the key molecular mechanisms involved in the pathogenesis of obesity could be beneficial for the development of a therapeutic approach. Hormones such as ghrelin, glucagon like peptide 1 (GLP-1) peptide YY (PYY), pancreatic polypeptide (PP), cholecystokinin (CCK) secreted by an endocrine organ gut, have an intense impact on energy balance and maintenance of homeostasis by inducing satiety and meal termination...
January 2016: Metabolism: Clinical and Experimental
Jessie A Elliott, Sabrina Jackson, Sinead King, Ruth McHugh, Neil G Docherty, John V Reynolds, Carel W le Roux
OBJECTIVES: To characterize the gut hormone profile and determine the effect of satiety gut hormone blockade on food intake in disease-free postesophagectomy patients. BACKGROUND: Improved oncologic outcomes for esophageal cancer have resulted in increased survivorship and a focus on health-related quality of life. Anorexia and early satiety are common, but putative causative factors, in particular the gut-brain hormonal axis, have not been systematically studied...
November 2015: Annals of Surgery
G Abdeen, C W le Roux
Various bariatric surgical procedures are effective at improving health in patients with obesity associated co-morbidities, but the aim of this review is to specifically describe the mechanisms through which Roux-en-Y gastric bypass (RYGB) surgery enables weight loss for obese patients using observations from both human and animal studies. Perhaps most but not all clinicians would agree that the beneficial effects outweigh the harm of RYGB; however, the mechanisms for both the beneficial and deleterious (for example postprandial hypoglycaemia, vitamin deficiency and bone loss) effects are ill understood...
February 2016: Obesity Surgery
Ana de Hollanda, Gregori Casals, Salvadora Delgado, Amanda Jiménez, Judith Viaplana, Antonio M Lacy, Josep Vidal
CONTEXT: Factors underlying variable weight loss (WL) after Roux-en-Y gastric bypass (RYGB) are poorly understood. OBJECTIVE: Our objective was to gain insight on the role of gastrointestinal hormones on poor WL maintenance (P-WLM) following RYGB. DESIGN AND PATIENTS: First, glucagon-like peptide-1 (GLP-1), peptide YY (PYY), and ghrelin responses to a standardized mixed liquid meal (SMLM) were compared between subjects with good WL (G-WL, n = 32) or P-WLM (n = 22)...
December 2015: Journal of Clinical Endocrinology and Metabolism
M E J Lean, D Malkova
The aim of this article is to review the research into the main peripheral appetite signals altered in human obesity, together with their modifications after body weight loss with diet and exercise and after bariatric surgery, which may be relevant to strategies for obesity treatment. Body weight homeostasis involves the gut-brain axis, a complex and highly coordinated system of peripheral appetite hormones and centrally mediated neuronal regulation. The list of peripheral anorexigenic and orexigenic physiological factors in both animals and humans is intimidating and expanding, but anorexigenic glucagon-like peptide 1 (GLP-1), cholecystokinin (CCK), peptide YY (PYY) and orexigenic ghrelin from the gastrointestinal tract, pancreatic polypeptide (PP) from the pancreas and anorexigenic leptin from adiposites remain the most widely studied hormones...
April 2016: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Kaare V Grunddal, Cecilia F Ratner, Berit Svendsen, Felix Sommer, Maja S Engelstoft, Andreas N Madsen, Jens Pedersen, Mark K Nøhr, Kristoffer L Egerod, Andrea R Nawrocki, Timothy Kowalski, Andrew D Howard, Steen Seier Poulsen, Stefan Offermanns, Fredrik Bäckhed, Jens J Holst, Birgitte Holst, Thue W Schwartz
The 2 gut hormones glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) are well known to be coexpressed, costored, and released together to coact in the control of key metabolic target organs. However, recently, it became clear that several other gut hormones can be coexpressed in the intestinal-specific lineage of enteroendocrine cells. Here, we focus on the anatomical and functional consequences of the coexpression of neurotensin with GLP-1 and PYY in the distal small intestine. Fluorescence-activated cell sorting analysis, laser capture, and triple staining demonstrated that GLP-1 cells in the crypts become increasingly multihormonal, ie, coexpressing PYY and neurotensin as they move up the villus...
January 2016: Endocrinology
Magdy El-Salhy, Trygve Hausken
Inflammatory bowel disease (IBD) includes three main disorders: ulcerative colitis, Crohn's disease, and microscopic colitis. The etiology of IBD is unknown and the current treatments are not completely satisfactory. Interactions between the gut neurohormones and the immune system are thought to play a pivot role in inflammation, especially in IBD. These neurohormones are believed to include members of the neuropeptide YY (NPY) family, which comprises NPY, peptide YY (PYY), and pancreatic polypeptide (PP). Understanding the role of these peptides may shed light on the pathophysiology of IBD and potentially yield an effective treatment tool...
February 2016: Neuropeptides
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