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Pyy and human

Anton M Pluschke, Barbara A Williams, Dagong Zhang, Stephen T Anderson, Eugeni Roura, Michael J Gidley
Acute and sustained soluble dietary fibre (SDF) consumption are both associated with improved glucose tolerance in humans and animal models (e.g. porcine). However, the effects on glucose tolerance in grower pigs, adapted to diets with a combination of SDF have not been studied previously. In this experiment, cereal SDF wheat arabinoxylan (AX) and oat β-glucan (BG) were fed individually and in combination to determine the effect on glucose tolerance in jugular vein catheterized grower pigs. Five groups of Large White male grower pigs were fed highly digestible diets containing either 10% AX, 10% BG, 5% AX with 5% BG, a model cereal whole wheat flour (WWF), or a control wheat starch diet (WS) with no SDF...
2018: PloS One
Iain R Tough, Sarah Forbes, Herbert Herzog, Robert M Jones, Thue W Schwartz, Helen M Cox
The lipid sensor GPR119 is highly expressed by enteroendocrine L-cells and pancreatic β-cells that release the hormones, PYY and GLP-1, and insulin, respectively. Endogenous oleoylethanolamide (OEA) and the dietary metabolite, 2-monoacylglycerol (2-OG) can each activate GPR119. Here we compared mucosal responses to selective, synthetic GPR119 agonists (AR440006, AR231453) and the lipids, OEA, 2-OG and N-oleoyldopamine (OLDA) monitoring epithelial ion transport as a read-out for L-cell activity in native mouse and human gastrointestinal (GI) mucosae...
February 19, 2018: Endocrinology
Patricio Atanes, Inmaculada Ruz-Maldonado, Ross Hawkes, Bo Liu, Min Zhao, Guo Cai Huang, Israa Mohammed Al-Amily, Albert Salehi, Stefan Amisten, Shanta J Persaud
INTRODUCTION: Islets synthesise and secrete numerous peptides, some of which are known to be important regulators of islet function and glucose homeostasis. In this study, we quantified mRNAs encoding all peptide ligands of islet G protein-coupled receptors (GPCRs) in isolated human and mouse islets and carried out in vitro islet hormone secretion studies to provide functional confirmation for the species-specific role of peptide YY (PYY) in mouse islets. MATERIALS AND METHODS: GPCR peptide ligand mRNAs in human and mouse islets were quantified by quantitative real-time PCR relative to the reference genes ACTB, GAPDH, PPIA, TBP and TFRC...
February 17, 2018: Cellular and Molecular Life Sciences: CMLS
Fiona M Gribble, Claire L Meek, Frank Reimann
A new strategy under development for the treatment of type 2 diabetes and obesity is to mimic some of the effects of bariatric surgery by delivering food-related stimuli to the distal gastrointestinal tract where they should enhance the release of gut hormones such as glucagon-like peptide-1 (GLP-1) and peptideYY (PYY). Methods include inhibition of food digestion and absorption in the upper GI tract, or oral delivery of stimuli in capsules or pelleted form to protect them against gastric degradation. A variety of agents have been tested in humans using capsules, microcapsules or pellets, delivering nutrients, bile acids, fatty acids and bitter compounds...
February 2018: Peptides
Bo Xu, Silvana Vasile, Soren Ostergaard, Johan F Paulsson, Jasna Pruner, Johan Aqvist, Birgitte S Wulff, Hugo Gutierrez-de-Teran, Dan Larhammar
Understanding the agonist-receptor interactions in the neuropeptide Y (NPY)/peptide YY (PYY) signaling system is fundamental for the design of novel modulators of appetite regulation. We report here a binding model for the native peptide agonist PYY to the human Y2 receptor based on computational and in vitro pharmacological analyses. The Molecular Dynamics (MD) simulations yielded a conserved binding orientation for the full PYY and five analogues truncated at the amino terminus, which were pharmacologically characterized...
January 24, 2018: Molecular Pharmacology
P Larraufie, C Martin-Gallausiaux, N Lapaque, J Dore, F M Gribble, F Reimann, H M Blottiere
Peptide-YY (PYY) and Glucagon-Like Peptide-1 (GLP-1) play important roles in the regulation of food intake and insulin secretion, and are of translational interest in the field of obesity and diabetes. PYY production is highest in enteroendocrine cells located in the distal intestine, mirroring the sites where high concentrations of short chain fatty acids (SCFAs) are produced by gut microbiota. We show here that propionate and butyrate strongly increased expression of PYY but not GCG in human cell line and intestinal primary culture models...
January 8, 2018: Scientific Reports
Brianna J Stubbs, Pete J Cox, Rhys D Evans, Malgorzata Cyranka, Kieran Clarke, Heidi de Wet
OBJECTIVE: The ketones d-β-hydroxybutyrate (BHB) and acetoacetate are elevated during prolonged fasting or during a "ketogenic" diet. Although weight loss on a ketogenic diet may be associated with decreased appetite and altered gut hormone levels, it is unknown whether such changes are caused by elevated blood ketones. This study investigated the effects of an exogenous ketone ester (KE) on appetite. METHODS: Following an overnight fast, subjects with normal weight (n = 15) consumed 1...
November 6, 2017: Obesity
Tina Jorsal, Nicolai A Rhee, Jens Pedersen, Camilla D Wahlgren, Brynjulf Mortensen, Sara L Jepsen, Jacob Jelsing, Louise S Dalbøge, Peter Vilmann, Hazem Hassan, Jakob W Hendel, Steen S Poulsen, Jens J Holst, Tina Vilsbøll, Filip K Knop
AIMS/HYPOTHESIS: Enteroendocrine K and L cells are pivotal in regulating appetite and glucose homeostasis. Knowledge of their distribution in humans is sparse and it is unknown whether alterations occur in type 2 diabetes. We aimed to evaluate the distribution of enteroendocrine K and L cells and relevant prohormone-processing enzymes (using immunohistochemical staining), and to evaluate the mRNA expression of the corresponding genes along the entire intestinal tract in individuals with type 2 diabetes and healthy participants...
September 28, 2017: Diabetologia
Claudia Guida, Laura J McCulloch, Mahdieh Godazgar, Sam D Stephen, Charlotte Baker, Davide Basco, Jiawen Dong, Duan Chen, Anne Clark, Reshma D Ramracheya
AIMS: The gut hormone peptide tyrosine tyrosine (PYY) is critical for maintaining islet integrity and restoring islet function following Roux-en-Y gastric bypass (RYGB). The expression of PYY and its receptors (NPYRs) in islets has been documented but not fully characterized. Modulation of islet PYY by the proteolytic enzyme dipeptidyl peptidase IV (DPP-IV) has not been investigated and the impact of DPP-IV inhibition on islet PYY function remains unexplored. Here we have addressed these gaps and their effects on glucose-stimulated insulin secretion (GSIS)...
September 11, 2017: Diabetes, Obesity & Metabolism
A Khalaf, C L Hoad, A Menys, A Nowak, S A Taylor, S Paparo, M Lingaya, Y Falcone, G Singh, R C Spiller, P A Gowland, L Marciani, G W Moran
BACKGROUND: Feeding triggers inter-related gastrointestinal (GI) motor, peptide and appetite responses. These are rarely studied together due to methodological limitations. Recent MRI advances allow pan-intestinal, non-invasive assessment of motility in the undisturbed gut. This study aimed to develop a methodology to assess pan-intestinal motility and transit in a single session using MRI and compare imaging findings to GI peptide responses to a test meal and symptoms in a healthy volunteer cohort...
August 31, 2017: Neurogastroenterology and Motility: the Official Journal of the European Gastrointestinal Motility Society
Uthra Rajamani, Andrew R Gross, Camille Ocampo, Allen M Andres, Roberta A Gottlieb, Dhruv Sareen
Persistent exposure to man-made endocrine disrupting chemicals during fetal endocrine development may lead to disruption of metabolic homeostasis contributing to childhood obesity. Limited cellular platforms exist to test endocrine disrupting chemical-induced developmental abnormalities in human endocrine tissues. Here we use an human-induced pluripotent stem cell-based platform to demonstrate adverse impacts of obesogenic endocrine disrupting chemicals in the developing endocrine system. We delineate the effects upon physiological low-dose exposure to ubiquitous endocrine disrupting chemicals including, perfluoro-octanoic acid, tributyltin, and butylhydroxytoluene, in endocrine-active human-induced pluripotent stem cell-derived foregut epithelial cells and hypothalamic neurons...
August 9, 2017: Nature Communications
A Alamshah, E Spreckley, M Norton, J S Kinsey-Jones, A Amin, A Ramgulam, Y Cao, R Johnson, K Saleh, E Akalestou, Z Malik, N Gonzalez-Abuin, A Jomard, R Amarsi, A Moolla, P R Sargent, G W Gray, S R Bloom, K G Murphy
OBJECTIVE: High-protein diets (HPDs) are associated with greater satiety and weight loss than diets rich in other macronutrients. The exact mechanisms by which HPDs exert their effects are unclear. However, evidence suggests that the sensing of amino acids produced as a result of protein digestion may have a role in appetite regulation and satiety. We investigated the effects of l-phenylalanine (L-Phe) on food intake and glucose homeostasis in rodents. METHODS: We investigated the effects of the aromatic amino-acid and calcium-sensing receptor (CaSR) agonist l-phenylalanine (L-Phe) on food intake and the release of the gastrointestinal (GI) hormones peptide YY (PYY), glucagon-like peptide-1 (GLP-1) and ghrelin in rodents, and the role of the CaSR in mediating these effects in vitro and in vivo...
November 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
Takeshi Yamasaki, Hideki Hirose, Tohru Yamashita, Nobuyuki Takakura, Sachie Morimoto, Takashi Nakahata, Asato Kina, Yoshihide Nakano, Yumiko Okano Tamura, Jun Sugama, Tomoyuki Odani, Yuji Shimizu, Shinji Iwasaki, Masanori Watanabe, Tsuyoshi Maekawa, Shizuo Kasai
Somatostatin (SST) is a peptide hormone comprising 14 or 28 amino acids that inhibits endocrine and exocrine secretion via five distinct G-protein-coupled receptors (SSTR1-5). SSTR5 has an important role in inhibiting the secretion of pancreatic and gastrointestinal hormones (e.g., insulin, GLP-1, PYY) through the binding of SSTs; hence, SSTR5 antagonists are expected to be novel anti-diabetic drugs. In the course of our lead generation program of SSTR5 antagonists, we have discovered a novel spiroazetidine derivative 3a...
August 1, 2017: Bioorganic & Medicinal Chemistry
Keyne Charlot, Cécile Faure, Sophie Antoine-Jonville
Understanding the regulation of human food intake in response to an acute exercise session is of importance for interventions with athletes and soldiers, as well as overweight individuals. However, the influence of hot and cold environments on this crucial function for the regulation of body mass and motor performance has not been summarized. The purpose of this review was to exhaustively search the literature on the effect of ambient temperature during an exercise session on the subsequent subjective feeling of appetite, energy intake (EI) and its regulation...
June 10, 2017: Nutrients
Nicolien C de Clercq, Myrthe N Frissen, Albert K Groen, Max Nieuwdorp
OBJECTIVE: Emerging preclinical evidence has shown that the bidirectional signaling between the gastrointestinal (GI) tract and the brain, the so-called gut-brain axis, plays an important role in both host metabolism and behavior. In this review, we discuss the potential mechanisms of the brain-gut axis in relation to the pathophysiology of metabolic syndrome. METHODS: A selective literature review was conducted to evaluate GI and brain interactions. RESULTS: Evidence suggests reduced microbial diversity in obesity and metabolic dysregulation...
October 2017: Psychosomatic Medicine
Emanuel E Canfora, Christina M van der Beek, Johan W E Jocken, Gijs H Goossens, Jens J Holst, Steven W M Olde Damink, Kaatje Lenaerts, Cornelis H C Dejong, Ellen E Blaak
Short-chain fatty acids (SCFA), formed by microbial fermentation, are believed to be involved in the aetiology of obesity and diabetes. This study investigated the effects of colonic administration of physiologically relevant SCFA mixtures on human substrate and energy metabolism. In this randomized, double-blind, crossover study, twelve normoglycaemic men (BMI 25-35 kg/m(2)) underwent four investigational days, during which SCFA mixtures (200 mmol/L) high in either acetate (HA), propionate (HP), butyrate (HB) or placebo (PLA) were rectally administered during fasting and postprandial conditions (oral glucose load)...
May 24, 2017: Scientific Reports
Jonna C Sandberg, Inger M E Björck, Anne C Nilsson
BACKGROUND: The prevalence of obesity is increasing worldwide and prevention is needed. Whole grain has shown potential to lower the risk of obesity, cardiovascular disease and type 2 diabetes. One possible mechanism behind the benefits of whole grain is the gut fermentation of dietary fiber (DF), e.g. non-starch polysaccharides and resistant starch (RS), in whole grain. The purpose of the study is to investigate the effect of whole grain rye-based products on glucose- and appetite regulation...
April 21, 2017: Nutrition Journal
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
Sonja Schiess, Stefanie Platz, Margrit Kemper, Monika Schreiner, Inga Mewis, Sascha Rohn, Christiane Bumke-Vogt, Olga Pivovarova, Andreas F H Pfeiffer
SCOPE: Nasturtium plants contain the glucosinolate glucotropaeolin and its corresponding breakdown product benzyl isothiocyanate (BITC), the latter being intensively studied with regard to cancer chemoprevention and anti-inflammatory properties. In addition, recent research has shown that isothiocyanates are able to activate the release of several gut hormones in vitro and in rodent studies. Here, we tested the effects of a dietary nasturtium administration on circulating levels of gut hormones in humans...
August 2017: Molecular Nutrition & Food Research
Katharina Kessler, Silke Hornemann, Klaus J Petzke, Margrit Kemper, Achim Kramer, Andreas F H Pfeiffer, Olga Pivovarova, Natalia Rudovich
Diurnal carbohydrate and fat distribution modulates glycaemic control in rodents. In humans, the optimal timing of both macronutrients and its effects on glycaemic control after prolonged consumption are not studied in detail. In this cross-over trial, 29 non-obese men were randomized to two four-week diets: (1) carbohydrate-rich meals until 13.30 and fat-rich meals between 16.30 and 22.00 (HC/HF) versus (2) inverse sequence of meals (HF/HC). After each trial period two meal tolerance tests were performed, at 09...
March 8, 2017: Scientific Reports
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