DOCSLIB.ORG

Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Combined GLP-1, Oxyntomodulin, and Peptide YY Improves Body EMERGING THERAPIES: DRUGS AND REGIMENS Diabetes Care 1 Preeshila Behary,1 George Tharakan,1 Combined GLP-1, Oxyntomodulin, Kleopatra Alexiadou,1 Nicholas Johnson,2 Nicolai J. Wewer Albrechtsen,3,4 and Peptide YY Improves Julia Kenkre,1 Joyceline Cuenco,1 David Hope,1 Oluwaseun Anyiam,1 Body Weight and Glycemia in Sirazum Choudhury,1 Haya Alessimii,1 Ankur Poddar,1 James Minnion,1 Obesity and Prediabetes/Type Chedie Doyle,1 Gary Frost,1 Carel Le Roux,1,5 Sanjay Purkayastha,6 Krishna Moorthy,6 2 Diabetes: A Randomized Waljit Dhillo,1 Jens J. Holst,7 Ahmed R. Ahmed,6 A. Toby Prevost,2 Single-Blinded Placebo Stephen R. Bloom,1 and Tricia M. Tan1 Controlled Study https://doi.org/10.2337/dc19-0449 OBJECTIVE 1Section of Investigative Medicine, Imperial Col- Roux-en-Y gastric bypass (RYGB) augments postprandial secretion of glucagon-like lege London, London, U.K. 2Imperial Clinical Trials Unit, Imperial College peptide 1 (GLP-1), oxyntomodulin (OXM), and peptide YY (PYY). Subcutaneous London, London, U.K. infusion of these hormones (“GOP”), mimicking postprandial levels, reduces energy 3Department of Clinical Biochemistry, Rigshospi- intake. Our objective was to study the effects of GOP on glycemia and body weight talet, Copenhagen, Denmark 4 when given for 4 weeks to patients with diabetes and obesity. Novo Nordisk Foundation Center for Protein Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Den- RESEARCH DESIGN AND METHODS mark In this single-blinded mechanistic study, obese patients with prediabetes/diabetes 5School of Medicine, University College Dublin, were randomized to GOP (n = 15) or saline (n = 11) infusion for 4 weeks. We also Dublin, Ireland 6 studied 21 patients who had undergone RYGB and 22 patients who followed a very Department of Surgery and Cancer, Imperial College Healthcare National Health Service Trust, low-calorie diet (VLCD) as unblinded comparators. Outcomes measured were 1) London, U.K. body weight, 2) fructosamine levels, 3) glucose and insulin during a mixed meal test 7Panum Institute, Department of Biomedical (MMT), 4) energy expenditure (EE), 5) energy intake (EI), and 6) mean glucose and Sciences and the Novo Nordisk Foundation Center measures of glucose variability during continuous glucose monitoring. for Basic Metabolic Research, University of Co- penhagen, Copenhagen, Denmark RESULTS Corresponding author: Tricia M. Tan, t.tan@ imperial.ac.uk GOP infusion was well tolerated over the 4-week period. There was a greater weight P 2 2 2 Received 5 March 2019 and accepted 25 April loss ( = 0.025) with GOP (mean change 4.4 [95% CI 5.3, 3.5] kg) versus saline 2019 2 2 2 P ( 2.5 [ 4.1, 0.9] kg). GOP led to a greater improvement ( = 0.0026) in fructosamine Clinical trial reg. no. NCT01945840, clinicaltrials (244.1 [262.7, 225.5] mmol/L) versus saline (211.7 [218.9, 24.5] mmol/L). Despite a .gov smaller weight loss compared with RYGB and VLCD, GOP led to superior glucose This article contains Supplementary Data online tolerance after a mixed-meal stimulus and reduced glycemic variability compared at http://care.diabetesjournals.org/lookup/suppl/ with RYGB and VLCD. doi:10.2337/dc19-0449/-/DC1. P.B. and G.T. contributed equally. CONCLUSIONS © 2019 by the American Diabetes Association. GOP infusion improves glycemia and reduces body weight. It achieves superior Readers may use this article as long as the work glucose tolerance and reduced glucose variability compared with RYGB and VLCD. is properly cited, the use is educational and not for profit, and the work is not altered. More infor- GOP is a viable alternative for the treatment of diabetes with favorable effects on mation is available at http://www.diabetesjournals body weight. .org/content/license. Diabetes Care Publish Ahead of Print, published online June 8, 2019 2 GOP Combination in Obesity and Type 2 Diabetes Diabetes Care Bariatric surgery, in particular Roux-en-Y of analogs possessing extended pharma- Dutch Eating Behavior Questionnaire gastric bypass (RYGB), remains the most cokinetics. Lastly, continuous subcuta- (DEBQ) questionnaires (18–20). efficacious treatment for obesity and neous infusions are commonplace in type 2 diabetes (T2DM). Glycemic im- diabetes treatment, demonstrating its Interventions provement after RYGB is superior to practicality in daily life. Infusion Groups (GOP or Saline) intensive medical management and is We therefore hypothesized that a GOP GLP-1 (7-36) amide, PYY (3-36) amide, sustained, with diabetes remission rates infusion, given for 4 weeks in “free living” and OXM were manufactured to Good of 26–29% at 5 years (1). Mechanistic conditions, would reduce body weight Manufacturing Practice standards (Am- studies have shown an early improve- and improve glycemia compared with bioPharm). They were mixed under ster- ment in hepatic insulin sensitivity and a placebo of 0.9% saline (hereafter re- ile conditions and freeze-dried in single later in peripheral insulin sensitivity as ferred to as Saline) infusion. To compare vials. Visually identical vials containing well as b-cell function (2). Proposed mech- the metabolic effects of GOP with those freeze-dried 0.9% Saline were also man- anisms include early postsurgical calorie of RYGB, we studied a group of patients ufactured. Vials were reconstituted with restriction; postprandial secretion of the who underwent surgery. To compare the sterile water for injections and added to satiety gut hormones glucagon-like pep- effects of GOP with simple dietary re- 0.9% Saline. Reconstituted peptides were fi tide 1 (GLP-1), oxyntomodulin (OXM), striction, we studied a group of patients veri ed to be stable for over 12 h at 37°C and peptide YY (PYY), reduced secretion who followed an 800 kcal/day very low- by high-performance liquid chromatog- of the orexigenic hormone ghrelin, bypass calorie diet (VLCD). raphy (Supplementary Fig. 1). A Cane of the proximal small bowel and reduced Crono Infusion pump (Applied Medical secretion of an “anti-incretin,” changes in RESEARCH DESIGN AND METHODS Technology) and an infusion set (Med- bile acid metabolism, changes in gut tronic) was used to deliver the subcuta- Study Design and Participants neous infusion of GOP at a dose of 4/4/ microbiota composition, reprogramming This mechanistic study took place at the 0.4 pmol/kg/min, respectively (5). Vol- of intestinal glucose metabolism, and in- National Institute for Health Research (NIHR) unteers were allocated to receive the crease in energy expenditure, among Imperial Clinical Research Unit Facility GOP or Saline infusion for 28 days by others (3). However, the exact contribu- at Hammersmith Hospital, London, from simple randomization performed by an tions from each mechanism are not clear. July 2016 to October 2018. It was a single- independent investigator. Volunteers’ GLP-1, OXM, and PYY are released blinded randomized controlled study usual treatment for diabetes was sus- from the L cells of the small intestine comparing two infusion groups (GOP pended for the duration of the study. and colon, and their postprandial secre- or Saline) in patients with obesity and Only volunteers remained blinded to the tion is augmented several-fold after prediabetesorT2DM.Twofurthersimilar nature of the infusion from allocation RYGB (4,5). GLP-1 is insulinotropic and nonblinded groups of patients under- until the end of the 28-day infusion period. reduces food intake. Its analogs are an going RYGB and patients following a They were instructed to run the infusion established treatment for diabetes (6) as VLCD diet were recruited. Potential vol- for 12 h/day, beginning 1 h before break- well as obesity (7). OXM is a dual agonist unteers for the GOP, Saline, and VLCD fast and disconnecting after their last meal of the GLP-1 and glucagon receptors (8), groups were recruited from clinics at the of the day. On study days, the infusions which reduces food intake (9) and in- Imperial Weight Centre (IWC) or from were commenced at least 2 h before any creases energy expenditure (10), leading newspaper advertising, whereas patients study procedures. All volunteers also re- to weight loss (11). PYY acts to reduce already listed for surgery at the IWC were appetite and food intake postprandially ceived dietetic advice on healthy eating recruited to form the RYGB group. fi (12,13). Combinations of GLP-1 and PYY and weight loss from a quali ed dietitian. (14,15), OXM and PYY (16), and GLP-1 and Inclusion and Exclusion Criteria RYGB Group glucagon (17) have synergistic effects on Key eligibility criteria were male or fe- Volunteers undergoing RYGB attended food intake. male participants aged between 18 and the research unit for a baseline visit before Replicating the postprandial gut hor- 70 years, meeting the U.K. National surgery and were reviewed at 2, 4, and 12 mone levels after RYGB is possible using Health Service (NHS) criteria for bariatric weeks after surgery. RYGB surgery was a continuous subcutaneous infusion of surgery, and with a diagnosis of predi- performed laparoscopically according to combination of GLP-1, OXM, and PYY abetes (impaired fasting glucose, im- standardized techniques by three desig- (“GOP”). This is safe, acceptable, and paired glucose tolerance, or HbA1c of nated surgeons at IWC. led to a reduction in total ad libitum 6.0–6.4% [42–47 mmol/mol]) or T2DM VLCD Group energy intake compared with placebo according to World Health Organization Volunteers attended the research unit for over a 10.5-h infusion (5). A continuous criteria. Patients who had diabetes had a baseline visit, before starting a complete subcutaneous infusion obviates the de- a stable HbA1c of #9.0% (75 mmol/mol) meal replacement VLCD of 800 kcal/day velopment of sharp peaks and leads to a either on diet or a single oral hypogly- for 4 weeks (Cambridge Weight Plan).
Load more

Recommended publications
  • The Impact of a Plant-Based Diet on Gestational Diabetes:A Review
    antioxidants Review The Impact of a Plant-Based Diet on Gestational Diabetes: A Review Antonio Schiattarella 1 , Mauro Lombardo 2 , Maddalena Morlando 1 and Gianluca Rizzo 3,* 1 Department of Woman, Child and General and Specialized Surgery, University of Campania “Luigi Vanvitelli”, 80138 Naples, Italy; [email protected] (A.S.); [email protected] (M.M.) 2 Department of Human Sciences and Promotion of the Quality of Life, San Raffaele Roma Open University, 00166 Rome, Italy; [email protected] 3 Independent Researcher, Via Venezuela 66, 98121 Messina, Italy * Correspondence: [email protected]; Tel.: +39-320-897-6687 Abstract: Gestational diabetes mellitus (GDM) represents a challenging pregnancy complication in which women present a state of glucose intolerance. GDM has been associated with various obstetric complications, such as polyhydramnios, preterm delivery, and increased cesarean delivery rate. Moreover, the fetus could suffer from congenital malformation, macrosomia, neonatal respiratory distress syndrome, and intrauterine death. It has been speculated that inflammatory markers such as tumor necrosis factor-alpha (TNF-α), interleukin (IL) 6, and C-reactive protein (CRP) impact on endothelium dysfunction and insulin resistance and contribute to the pathogenesis of GDM. Nutritional patterns enriched with plant-derived foods, such as a low glycemic or Mediterranean diet, might favorably impact on the incidence of GDM. A high intake of vegetables, fibers, and fruits seems to decrease inflammation by enhancing antioxidant compounds. This aspect contributes to improving insulin efficacy and metabolic control and could provide maternal and neonatal health benefits. Our review aims to deepen the understanding of the impact of a plant-based diet on Citation: Schiattarella, A.; Lombardo, oxidative stress in GDM.
    [Show full text]
  • Searching for Novel Peptide Hormones in the Human Genome Olivier Mirabeau
    Searching for novel peptide hormones in the human genome Olivier Mirabeau To cite this version: Olivier Mirabeau. Searching for novel peptide hormones in the human genome. Life Sciences [q-bio]. Université Montpellier II - Sciences et Techniques du Languedoc, 2008. English. tel-00340710 HAL Id: tel-00340710 https://tel.archives-ouvertes.fr/tel-00340710 Submitted on 21 Nov 2008 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. UNIVERSITE MONTPELLIER II SCIENCES ET TECHNIQUES DU LANGUEDOC THESE pour obtenir le grade de DOCTEUR DE L'UNIVERSITE MONTPELLIER II Discipline : Biologie Informatique Ecole Doctorale : Sciences chimiques et biologiques pour la santé Formation doctorale : Biologie-Santé Recherche de nouvelles hormones peptidiques codées par le génome humain par Olivier Mirabeau présentée et soutenue publiquement le 30 janvier 2008 JURY M. Hubert Vaudry Rapporteur M. Jean-Philippe Vert Rapporteur Mme Nadia Rosenthal Examinatrice M. Jean Martinez Président M. Olivier Gascuel Directeur M. Cornelius Gross Examinateur Résumé Résumé Cette thèse porte sur la découverte de gènes humains non caractérisés codant pour des précurseurs à hormones peptidiques. Les hormones peptidiques (PH) ont un rôle important dans la plupart des processus physiologiques du corps humain.
    [Show full text]
  • Effects of Dietary Macronutrients on Appetite-Related Hormones in Blood on Body Composition of Lean and Obese Rats
    Animal Industry Report Animal Industry Report AS 652 ASL R2081 2006 Effects of Dietary Macronutrients on Appetite-Related Hormones in Blood on Body Composition of Lean and Obese Rats Michelle Bohan Iowa State University Lloyd L. Anderson Iowa State University Allen H. Trenkle Iowa State University Donald C. Beitz Iowa State University Follow this and additional works at: https://lib.dr.iastate.edu/ans_air Part of the Agriculture Commons, and the Animal Sciences Commons Recommended Citation Bohan, Michelle; Anderson, Lloyd L.; Trenkle, Allen H.; and Beitz, Donald C. (2006) "Effects of Dietary Macronutrients on Appetite-Related Hormones in Blood on Body Composition of Lean and Obese Rats ," Animal Industry Report: AS 652, ASL R2081. DOI: https://doi.org/10.31274/ans_air-180814-908 Available at: https://lib.dr.iastate.edu/ans_air/vol652/iss1/22 This Companion Animal is brought to you for free and open access by the Animal Science Research Reports at Iowa State University Digital Repository. It has been accepted for inclusion in Animal Industry Report by an authorized editor of Iowa State University Digital Repository. For more information, please contact [email protected]. Iowa State University Animal Industry Report 2006 Effects of Dietary Macronutrients on Appetite-Related Hormones in Blood on Body Composition of Lean and Obese Rats A.S. Leaflet R2081 ghrelin. Ghrelin is an antagonist of leptin by acting upon the neuropeptide Y/Y1 receptor pathway. Leptin causes Michelle Bohan, graduate student of biochemistry; satiety, whereas ghrelin stimulates nutrient intake. Leptin Lloyd Anderson, distinguished professor of animal science; and ghrelin thereby regulate the action of each other.
    [Show full text]
  • Secretin and Autism: a Clue but Not a Cure
    SCIENCE & MEDICINE Secretin and Autism: A Clue But Not a Cure by Clarence E. Schutt, Ph.D. he world of autism has been shaken by NBC’s broadcast connections could not be found. on Dateline of a film segment documenting the effect of Tsecretin on restoring speech and sociability to autistic chil- The answer was provided nearly one hundred years ago by dren. At first blush, it seems unlikely that an intestinal hormone Bayless and Starling, who discovered that it is not nerve signals, regulating bicarbonate levels in the stomach in response to a but rather a novel substance that stimulates secretion from the good meal might influence the language centers of the brain so cells forming the intestinal mucosa. They called this substance profoundly. However, recent discoveries in neurobiology sug- “secretin.” They suggested that there could be many such cir- gest several ways of thinking about the secretin-autism connec- culating substances, or molecules, and they named them “hor- tion that could lead to the breakthroughs we dream about. mones” based on the Greek verb meaning “to excite”. As a parent with more than a decade of experience in consider- A simple analogy might help. If the body is regarded as a commu- ing a steady stream of claims of successful treatments, and as a nity of mutual service providers—the heart and muscles are the pri- scientist who believes that autism is a neurobiological disorder, I mary engines of movement, the stomach breaks down foods for have learned to temper my hopes about specific treatments by distribution, the liver detoxifies, and so on—then the need for a sys- seeing if I could construct plausible neurobiological mechanisms tem of messages conveyed by the blood becomes clear.
    [Show full text]
  • Glucagon and Gastrointestinal Motility in Relation to Thyroid-Parathyroid Function
    Upsala J Med Sci 77: 183-188, 1972 Glucagon and Gastrointestinal Motility in Relation to Thyroid-Parathyroid Function HENRY JOHANSSON and ANDERS SEGERSTROM From the Department of Surgery, University Hospital, Uppsala, Sweden ABSTRACT MATERIAL Gastrointestinal propulsive motility was studied after The material consisted of 109 male albino rats (Sprague- inhgastric deposition of a non-absorbable isotope in Dawley) fed on laboratory food and with free access to rats after subcutaneous glucagon injections. Glucagon water. The animals were distributed at random in fol- administration was followed by retardation of gastric lowing series: emptying. The results indicated that the retarding effect Series I of glucagon on gastrointestinal propulsion was independent The influence of glucagon on gastrointestinal motility in of the presence of both thyroid and parathyroid tissue. intact rats. The observation period was 7 days. The hypocalcemic effect of glucagon was exerted in- dependently of the presence of thyroid tissue, Le. thyro- 1. Intact rats given 1.2 mg glucagon/kg body weight calcitonin. (GN-A, n= 6) 2. Intact rats given 4.8 mg glucagon/kg body weight (GN-B, n= 5) 3. Intact rats given 9.6 mg glucagon/kg body weight INTRODUCTION (GN-C, n= 12) 4. Intact rats given glucine buffert (GLY, n= 10). Glucagon is known to influence gastrointestinal Series I1 motility. In man, Dotevall & Kock (2) observed The influence of glucagon on gastrointestinal motility in that glucagon retarded gastrointestinal motility parathyroidectomized rats. The animals were given 4.8 independently of the hyperglucemia. In dogs, mg glucagon/kg body weight. The observation period glucagon retarded motility of the stomach ani was 90 days.
    [Show full text]
  • AVP-Induced Counter-Regulatory Glucagon Is Diminished in Type 1 Diabetes
    bioRxiv preprint doi: https://doi.org/10.1101/2020.01.30.927426; this version posted January 31, 2020. The copyright holder for this preprint (which was not certified by peer review) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under aCC-BY 4.0 International license. AVP-induced counter-regulatory glucagon is diminished in type 1 diabetes Angela Kim1,2, Jakob G. Knudsen3,4, Joseph C. Madara1, Anna Benrick5, Thomas Hill3, Lina Abdul Kadir3, Joely A. Kellard3, Lisa Mellander5, Caroline Miranda5, Haopeng Lin6, Timothy James7, Kinga Suba8, Aliya F. Spigelman6, Yanling Wu5, Patrick E. MacDonald6, Ingrid Wernstedt Asterholm5, Tore Magnussen9, Mikkel Christensen9,10,11, Tina Vilsboll9,10,12, Victoria Salem8, Filip K. Knop9,10,12,13, Patrik Rorsman3,5, Bradford B. Lowell1,2, Linford J.B. Briant3,14,* Affiliations 1Division of Endocrinology, Diabetes, and Metabolism, Beth Israel Deaconess Medical Center, Boston, MA 02215, USA. 2Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA. 3Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford, OX4 7LE, UK. 4Section for Cell Biology and Physiology, Department of Biology, University of Copenhagen. 5Institute of Neuroscience and Physiology, Metabolic Research Unit, University of Göteborg, 405 30, Göteborg, Sweden. 6Alberta Diabetes Institute, 6-126 Li Ka Shing Centre for Health Research Innovation, Edmonton, Alberta, T6G 2E1, Canada. 7Department of Clinical Biochemistry, John Radcliffe, Oxford NHS Trust, OX3 9DU, Oxford, UK. 8Section of Cell Biology and Functional Genomics, Department of Metabolism, Digestion and Reproduction, Imperial College London, W12 0NN, UK.
    [Show full text]
  • Localization of Glucokinase Gene Expression in the Rat Brain Ronald M
    Localization of Glucokinase Gene Expression in the Rat Brain Ronald M. Lynch, Linda S. Tompkins, Heddwen L. Brooks, Ambrose A. Dunn-Meynell, and Barry E. Levin The brain contains a subpopulation of glucosensing neu- rons that alter their firing rate in response to elevated glucose concentrations. In pancreatic ␤-cells, gluco- ammalian feeding behavior and general energy kinase (GK), the rate-limiting enzyme in glycolysis, medi- homeostasis appear to be regulated by circu- ates glucose-induced insulin release by regulating intra- lating levels of nutrients (glucose) and pep- cellular ATP production. A similar role for GK is pro- tides (e.g., leptin, insulin). Sensors to detect lev- posed to underlie neuronal glucosensing. Via in situ M els of these factors have been found to reside within specific hybridization, GK mRNA was localized to hypothalamic areas that are thought to contain relatively large popu- nuclei of the hypothalamus (1–8), where central regulation of lations of glucosensing neurons (the arcuate, ventrome- energy homeostasis is believed to be coordinated. For exam- dial, dorsomedial, and paraventricular nuclei and the lat- ple, large changes in blood glucose are correlated with cen- eral area). GK also was found in brain areas without trally mediated responses such as thermogenesis through known glucosensing neurons (the lateral habenula, the activation of the sympathetic nervous system. These changes bed nucleus stria terminalis, the inferior olive, the are monitored by the brain (9–11), and such responses are retrochiasmatic and medial preoptic areas, and the thal- altered in obesity-prone animals (11–13). Moreover, lesions amic posterior paraventricular, interpeduncular, oculo- of the ventromedial hypothalamus (VMH) prevent the hypo- motor, and anterior olfactory nuclei).
    [Show full text]
  • And Oxytocin-Induced Glucagon Secretion in V1b Vasopressin Receptor Knockout Mice
    361 Mutual regulation of vasopressin- and oxytocin-induced glucagon secretion in V1b vasopressin receptor knockout mice Yoko Fujiwara, Masami Hiroyama, Atsushi Sanbe, Junji Yamauchi, Gozoh Tsujimoto1 and Akito Tanoue Department of Pharmacology, National Research Institute for Child Health and Development, 2-10-1 Okura, Setagaya-ku, Tokyo 157-8535, Japan 1Department of Genomic Drug Discovery Science, Graduate School of Pharmaceutical Sciences, Kyoto University Faculty of Pharmaceutical Sciences, Kyoto University, Yoshida Shimoadachi-cho, Sakyo-ku, Kyoto 606-8501, Japan (Requests for offprints should be addressed to A Tanoue; Email: [email protected]) Abstract [Arg8]-vasopressin (AVP) and oxytocin (OT) are neurohy- CL-14-26 further inhibited AVP- and OT-induced glucagon pophysial hormones which exert various actions, including secretions in islets of V1bRC/C mice (57 and 69% of the the control of blood glucose, in some peripheral tissues. To stimulation values respectively). In addition, both AVP and investigate the type of receptors involved in AVP- and OT stimulated glucagon secretion with the same efficacy in OT-induced glucagon secretion, we investigated the effect V1bRK/K mice as in V1bRC/C mice. AVP- and of these peptides on glucagon secretion in islets of OT-induced glucagon secretion in V1bRK/K mice was wild-type (V1bRC/C) and vasopressin V1b receptor significantly inhibited by CL-14-26. These results demonstrate knockout (V1bRK/K) mice. AVP-induced glucagon that V1b receptors can mediate OT-induced glucagon secretion secretion was significantly inhibited by the selective V1b and OTreceptors can mediate AVP-induced glucagon secretion receptor antagonist, SSR149415 (30%), and OT-induced in islets from V1bRC/C mice in the presence of a heterologous glucagon secretion by the specific OT receptor antagonist, antagonist, while AVP and OT can stimulate glucagon secretion ð Þ ½ ð Þ2; 4; 9 d CH2 5 Tyr Me Thr Tyr-NH2 OVT (CL-14-26) through the OTreceptors in V1bRK/K mice, suggesting that C C (45%), in islets of V1bR / mice.
    [Show full text]
  • Glucagon-Like Peptide 1 Secretion by the L-Cell the View from Within Gareth E
    Glucagon-Like Peptide 1 Secretion by the L-Cell The View From Within Gareth E. Lim1 and Patricia L. Brubaker1,2 Glucagon-like peptide 1 (GLP-1) is a gut-derived peptide GLP-1 receptor antagonists as well as GLP-1 receptor null secreted from intestinal L-cells after a meal. GLP-1 has mice have demonstrated that GLP-1 makes an essential numerous physiological actions, including potentiation of contribution to the “incretin” effect after a meal (3,4). glucose-stimulated insulin secretion, enhancement of However, GLP-1 secretion is reduced in patients with type ␤-cell growth and survival, and inhibition of glucagon 2 diabetes (5–7), and this may contribute in part to the release, gastric emptying, and food intake. These antidia- reduced incretin effect and the hyperglycemia that is betic effects of GLP-1 have led to intense interest in the use observed in these individuals (8). Thus, interest has now of this peptide for the treatment of patients with type 2 focused on the factors that regulate the release of this diabetes. Oral nutrients such as glucose and fat are potent physiological regulators of GLP-1 secretion, but non-nutri- peptide after nutrient ingestion. Many different GLP-1 ent stimulators of GLP-1 release have also been identified, secretagogues have been described in the literature over including the neuromodulators acetylcholine and gastrin- the past few decades, including nutrients, neurotransmit- releasing peptide. Peripheral hormones that participate in ters, neuropeptides, and peripheral hormones (rev. in energy homeostasis, such as leptin, have also been impli- 9,10). However, the specific receptors, ion channels, and cated in the regulation of GLP-1 release.
    [Show full text]
  • Biomoleculesbiomolecules
    1414Unit Objectives BiomoleculesBiomolecules After studying this Unit, you will be able to • explain the characteristics of “It is the harmonious and synchronous progress of chemical biomolecules like carbohydrates, reactions in body which leads to life”. proteins and nucleic acids and hormones; • classify carbohydrates, proteins, A living system grows, sustains and reproduces itself. nucleic acids and vitamins on the The most amazing thing about a living system is that it basis of their structures; is composed of non-living atoms and molecules. The • explain the difference between pursuit of knowledge of what goes on chemically within DNA and RNA; a living system falls in the domain of biochemistry. Living • describe the role of biomolecules systems are made up of various complex biomolecules in biosystem. like carbohydrates, proteins, nucleic acids, lipids, etc. Proteins and carbohydrates are essential constituents of our food. These biomolecules interact with each other and constitute the molecular logic of life processes. In addition, some simple molecules like vitamins and mineral salts also play an important role in the functions of organisms. Structures and functions of some of these biomolecules are discussed in this Unit. 14.114.114.1 Carbohydrates Carbohydrates are primarily produced by plants and form a very large group of naturally occurring organic compounds. Some common examples of carbohydrates are cane sugar, glucose, starch, etc. Most of them have a general formula, Cx(H2O)y, and were considered as hydrates of carbon from where the name carbohydrate was derived. For example, the molecular formula of glucose (C6H12O6) fits into this general formula, C6(H2O)6. But all the compounds which fit into this formula may not be classified as carbohydrates.
    [Show full text]
  • Anti-Obesity Therapy: from Rainbow Pills to Polyagonists
    1521-0081/70/4/712–746$35.00 https://doi.org/10.1124/pr.117.014803 PHARMACOLOGICAL REVIEWS Pharmacol Rev 70:712–746, October 2018 Copyright © 2018 The Author(s). This is an open access article distributed under the CC BY Attribution 4.0 International license. ASSOCIATE EDITOR: BIRGITTE HOLST Anti-Obesity Therapy: from Rainbow Pills to Polyagonists T. D. Müller, C. Clemmensen, B. Finan, R. D. DiMarchi, and M. H. Tschöp Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany (T.D.M., C.C., M.H.T.); German Center for Diabetes Research, Neuherberg, Germany (T.D.M., C.C., M.H.T.); Department of Chemistry, Indiana University, Bloomington, Indiana (B.F., R.D.D.); and Division of Metabolic Diseases, Technische Universität München, Munich, Germany (M.H.T.) Abstract ....................................................................................713 I. Introduction . ..............................................................................713 II. Bariatric Surgery: A Benchmark for Efficacy ................................................714 III. The Chronology of Modern Weight-Loss Pharmacology . .....................................715 A. Thyroid Hormones ......................................................................716 B. 2,4-Dinitrophenol .......................................................................716 C. Amphetamines. ........................................................................717 Downloaded from 1. Methamphetamine
    [Show full text]
  • Gastrointestinal Regulation of Food Intake
    Gastrointestinal regulation of food intake David E. Cummings, Joost Overduin J Clin Invest. 2007;117(1):13-23. https://doi.org/10.1172/JCI30227. Review Series Despite substantial fluctuations in daily food intake, animals maintain a remarkably stable body weight, because overall caloric ingestion and expenditure are exquisitely matched over long periods of time, through the process of energy homeostasis. The brain receives hormonal, neural, and metabolic signals pertaining to body-energy status and, in response to these inputs, coordinates adaptive alterations of energy intake and expenditure. To regulate food consumption, the brain must modulate appetite, and the core of appetite regulation lies in the gut-brain axis. This Review summarizes current knowledge regarding the neuroendocrine regulation of food intake by the gastrointestinal system, focusing on gastric distention, intestinal and pancreatic satiation peptides, and the orexigenic gastric hormone ghrelin. We highlight mechanisms governing nutrient sensing and peptide secretion by enteroendocrine cells, including novel taste- like pathways. The increasingly nuanced understanding of the mechanisms mediating gut-peptide regulation and action provides promising targets for new strategies to combat obesity and diabetes. Find the latest version: https://jci.me/30227/pdf Review series Gastrointestinal regulation of food intake David E. Cummings and Joost Overduin Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, University of Washington, Veterans Affairs Puget Sound Health Care System, Seattle, Washington, USA. Despite substantial fluctuations in daily food intake, animals maintain a remarkably stable body weight, because overall caloric ingestion and expenditure are exquisitely matched over long periods of time, through the process of energy homeostasis. The brain receives hormonal, neural, and metabolic signals pertaining to body-energy status and, in response to these inputs, coordinates adaptive alterations of energy intake and expenditure.
    [Show full text]