DOCSLIB.ORG

Microencapsulation of Tributyrin to Improve Sensory Qualities and Intestinal Delivery

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Microencapsulation of Tributyrin to Improve Sensory Qualities and Intestinal Delivery © 2015 Joseph Donald Donovan MICROENCAPSULATION OF TRIBUTYRIN TO IMPROVE SENSORY QUALITIES AND INTESTINAL DELIVERY BY JOSEPH DONALD DONOVAN DISSERTATION Submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Food Science and Human Nutrition with a concentration in Food Science in the Graduate College of the University of Illinois at Urbana-Champaign, 2015 Urbana, Illinois Doctoral Committee: Associate Professor Michael J. Miller, Chair Associate Professor Soo-Yeun Lee, Co-Director of Research Assistant Professor Youngsoo Lee, Co-Director of Research Professor Keith R. Cadwallader Professor Emeritus George C. Fahey, Jr. ABSTRACT Microencapsulation is commonly used in the food industry to provide functional and sensory benefits to a variety of compounds. Tributyrin (TB), a source of butyric acid, is characterized by a highly bitter taste and negative odor attributes. Its use in the maintenance of intestinal health and treatment of intestinal disorders shows promise. However, due to the negative sensory qualities and necessity to target the intestinal epithelium, TB has yet to be widely utilized in a food system for treatment. The overall objectives of this study were to: 1) determine the impact of protein type, inulin chain length, and gamma-cyclodextrin (GCD) on the stability and retention of microencapsulated TB, 2) measure which TB microcapsule formulation imparts the least overall sensory difference in an infant formula system, 3) determine the site of intestinal delivery and release of butyrate from microencapsulated TB, and 4) determine the sensory properties of food products containing microencapsulated TB. Microencapsulated TB in whey protein isolate (WPI)-based microcapsules resulted in higher (p<0.001) retention than soy protein isolate (SPI)-based microcapsules. The inclusion of inulin WPI-based wall materials improved (p<0.01) the retention of TB for all chain lengths over WPI-based microcapsules without inulin. The creation of altered surface morphology from inulin is due to the ability of inulin to interact with the WPI-based wall material. This interaction creates added wall flexibility during drying and may be responsible for increased TB retention. The use of GCD resulted in the highest TB retention (95%) when oven dried but the lowest when spray dried (62%). In infant formulas, GCD and TB oven dried (GCT OD) microcapsules were able to reduce the sensory perception of TB to a level indistinguishable from a control infant formula containing no TB. All other WPI, WPI-inulin, and GCD-based microcapsules were significantly different from the control (R-index above 57% or at p<0.05) but not from free TB (p>0.05) as indicated by the ii rating method. During in vitro digestion, all microcapsules containing TB showed limited butyrate release (<5%) during oral and gastric stages. In then simulated small intestine, TB microcapsules released approximately 75% of their total butyrate content with no significant differences (p>0.05) across formulations. During fermentation, GCD-based microcapsules produced significantly more butyrate (p<0.001) on a molar basis than all WPI-based microcapsules. The microcapsule GCT OD was able to effectively deliver and produce butyrate in the small and large intestines. Results from the descriptive analysis (DA) test conducted using GCT OD in apple sauce, infant formula, and crackers, revealed that GCT OD behaved differently in each system due to the matricies physical properties. Combined common attribute principal correlation analysis (PCA) biplots show samples containing free TB were highly characterized by bitter taste and aftertaste. Cracker samples were not significantly different (p>0.05) for all measured attributes intensities as compared to free TB-containing samples, and were significantly higher in bitter taste and aftertaste. Apple sauce and infant formula containing GCT OD were significantly (p<0.05) reduced in bitter taste and aftertaste as compared to free TB samples. This bitter taste and aftertaste intensity for GCT OD was still, however, significantly higher (p<0.05) than the control for apple sauce and infant formula. The inclusion of GCT OD in infant formula had the least overall impact on the attributes that characterize control infant formula samples. Overall, findings from this research can be used to guide the production and application of microencapsulated TB for use in these and additional food products for the potential improvement of intestinal health or disease states. Key Words: microencapsulation; spray drying; whey protein isolate; soy protein isolate; gamma-cyclodextrin; complexation; tributyrin; butyric acid; sensory evaluation; R-index; in vitro digestion; targeted release; descriptive analysis. iii ACKNOWLEDGEMENTS Firstly, I thank Dr. Soo-Yeun Lee and Dr. Youngsoo Lee for their support and encouragement throughout my graduate career at the University of Illinois. I came to this University searching for a chance to develop myself into the type of scientist and educator I saw in these two upon my arrival here. From the very start, their unrelenting support of my project and belief in me as a researcher are the only reasons this dissertation is possible. Thank you both for encouraging me to develop my skills as a scientist, an educator and a leader Secondly, thank you to my committee members: Dr. George C. Fahey Jr., Dr. Michael Miller, and Dr. Keith Cadwallader. From the moment my research began, it was apparent that the guidance and expertise of individuals with backgrounds different than my own was going to be necessary. With your help and guidance, we have been able to accomplish something much greater than we could have alone. Additionally, thank you to companies such as Hilmar Cheese Company and Wacker Chemie for their guidance and generous donation of research materials. I also thank the entire department of Food Science and Human Nutrition. Thank you to all the graduate students, staff, and faculty for your support. Also, thank you to my past and present lab mates and undergraduate researchers. Graduate school is not a journey anyone can do alone. I am indebted to you for the friendship, kindness, and support you have shown me. Finally, the biggest thank you of all is directed towards my Dad (Joe), Mom (Helen), and two sisters (Erin and Kathy). I truly am the luckiest person in the world for having your unconditional love in my life. Thank you for believing in me when I didn’t, and for picking me up when I fell down. Thank you to my extended family and friends near and far who are too many to name; I am so lucky to have each and every one of you in my life. iv Table of Contents List of Tables ................................................................................................................................. ix List of Figures ............................................................................................................................... .xi Chapter 1: Introduction ................................................................................................................... 1 1.1 Research background ............................................................................................................. 1 1.2 Research rationale and significance ...................................................................................... 4 1.3 Overall goal and central hypothesis ....................................................................................... 5 1.4 Specific research aims, hypotheses, and approaches ............................................................. 5 1.5 References ............................................................................................................................. 8 Chapter 2: Literature Review ........................................................................................................ 12 2.1 Microencapsulation ............................................................................................................. 12 2.2 Stability characterization and sensory testing in food products containing microencapsulants ..................................................................................................................... 19 2.3 Butyrate and tributyrin: functions in intestinal health ......................................................... 48 2.4 Model gastrointestinal systems ............................................................................................ 53 2.5 Sensory evaluation techniques in descriptive analysis and difference testing .................... 57 2.6 References ........................................................................................................................... 64 2.7 Tables and figures ................................................................................................................ 82 Chapter 3: Development and Analysis of Microencapsulated Tributyrin .................................... 84 3.1 Abstract ................................................................................................................................ 84 3.2 Introduction ......................................................................................................................... 85 3.3 Materials and methods ......................................................................................................... 90 3.4 Results and discussion ........................................................................................................
Load more

Recommended publications
  • Amended Safety Assessment of Triglycerides As Used in Cosmetics
    Amended Safety Assessment of Triglycerides as Used in Cosmetics Status: Re-Review for Panel Review Release Date: March 17, 2017 Panel Meeting Date: April 10-11, 2017 The 2017 Cosmetic Ingredient Review Expert Panel members are: Chairman, Wilma F. Bergfeld, M.D., F.A.C.P.; Donald V. Belsito, M.D.; Ronald A. Hill, Ph.D.; Curtis D. Klaassen, Ph.D.; Daniel C. Liebler, Ph.D.; James G. Marks, Jr., M.D., Ronald C. Shank, Ph.D.; Thomas J. Slaga, Ph.D.; and Paul W. Snyder, D.V.M., Ph.D. The CIR Director is Lillian J. Gill, D.P.A. This safety assessment was prepared by Monice M. Fiume, Assistant Director/Senior Scientific Analyst/Writer, and Bart Heldreth, Chemist. © Cosmetic Ingredient Review 1620 L Street, NW, Suite 1200 ♢ Washington, DC 20036-4702 ♢ ph 202.331.0651 ♢ fax 202.331.0088 ♢ [email protected] Commitment & Credibility since 1976 Memorandum To: CIR Expert Panel Members and Liaisons From: Monice M. Fiume MMF Assistant Director/Senior Scientific Analyst Date: March 17, 2017 Subject: Amended Safety Assessment of Triglycerides as Used in Cosmetics Enclosed is the Safety Assessment of Triglycerides as Used in Cosmetics. (It is identified as trygly042017rep in the pdf document.) This is a re-review that is being initiated in accord with CIR’s Procedures to reassess previously- reviewed conclusions after a period of 15 years. In 2000, the Panel published a safety assessment of Trihydroxystearin with the conclusion, “Based on the available animal and clinical data, which included summary data from the CIR safety assessments of Hydroxystearic Acid and Glyceryl Stearate and Glyceryl Stearate SE, the Panel concluded that Trihydroxystearin is safe as used in cosmetics.” In 2015, the Panel re-evaluated the safety of Hydroxystearic Acid and Glyceryl Stearate and Glyceryl Stearate SE, reaffirming that Hydroxystearic Acid is safe as a cosmetic ingredient in the present practices of use and concluding that Glyceryl Stearate and Glyceryl Stearate SE are safe in the present practices of use and concentration.
    [Show full text]
  • Nonionic Microemulsions As Solubilizers of Hydrophobic Drugs: Solubilization of Paclitaxel
    materials Article Nonionic Microemulsions as Solubilizers of Hydrophobic Drugs: Solubilization of Paclitaxel Jen-Ting Lo 1, Tzer-Min Lee 2 and Bing-Hung Chen 1,* 1 Department of Chemical Engineering, National Cheng Kung University, Tainan 70101, Taiwan; [email protected] 2 Institute of Oral Medicine, National Cheng Kung University, Tainan 70101, Taiwan; [email protected] * Correspondence: [email protected] or [email protected]; Tel.: +886-6-275-7575 (ext. 62695) Academic Editors: James Z. Tang and Charley Chuan-yu Wu Received: 14 July 2016; Accepted: 2 September 2016; Published: 7 September 2016 Abstract: The strategy using nonionic microemulsion as a solubilizer for hydrophobic drugs was studied and is demonstrated in this work. The aqueous phase behaviors of mixed nonionic surfactants with various oils at 37 ◦C are firstly constructed to give the optimal formulations of nonionic microemulsions with applications in the enhanced solubilization of the model hydrophobic drug, paclitaxel, at 37 ◦C. Briefly, the suitable oil phase with paclitaxel significantly dissolved is microemulsified with appropriate surfactants. Surfactants utilized include Tween 80, Cremophor EL, and polyethylene glycol (4.3) cocoyl ether, while various kinds of edible oils and fatty esters are used as the oil phase. On average, the apparent solubility of paclitaxel is increased to ca. 70–100 ppm in the prepared microemulsions at 37 ◦C using tributyrin or ethyl caproate as the oil phases. The sizes of the microemulsions attained are mostly from ca. 60 nm to ca. 200 nm. The cytotoxicity of the microemulsion formulations is assessed with the cellular viability of 3T3 cells.
    [Show full text]
  • Targeting Gut–Liver Axis for Treatment of Liver Fibrosis and Portal Hypertension
    Review Targeting Gut–Liver Axis for Treatment of Liver Fibrosis and Portal Hypertension Eric Kalo 1 , Scott Read 1,2,3,† and Golo Ahlenstiel 1,2,3,*,† 1 Blacktown Clinical School, School of Medicine, Western Sydney University, Blacktown, NSW 2148, Australia; [email protected] (E.K.); [email protected] (S.R.) 2 Blacktown Hospital, Blacktown, NSW 2148, Australia 3 Storr Liver Centre, The Westmead Institute for Medical Research, University of Sydney, Westmead, NSW 2145, Australia * Correspondence: [email protected]; Tel.: +61-2-9851-6073; Fax: +61-2-9851-6050 † These authors contribute equally to this work. Abstract: Antifibrotic therapies for the treatment of liver fibrosis represent an unconquered area of drug development. The significant involvement of the gut microbiota as a driving force in a multitude of liver disease, be it pathogenesis or fibrotic progression, suggest that targeting the gut–liver axis, relevant signaling pathways, and/or manipulation of the gut’s commensal microbial composition and its metabolites may offer opportunities for biomarker discovery, novel therapies and personalized medicine development. Here, we review potential links between bacterial translocation and deficits of host-microbiome compartmentalization and liver fibrosis that occur in settings of advanced chronic liver disease. We discuss established and emerging therapeutic strategies, translated from our current knowledge of the gut–liver axis, targeted at restoring intestinal eubiosis, ameliorating hepatic fibrosis and rising portal hypertension that characterize and define the course of decompensated cirrhosis. Keywords: liver fibrosis; portal hypertension; microbiota; cirrhosis; chronic liver disease; gut–liver Citation: Kalo, E.; Read, S.; Ahlenstiel, G. Targeting Gut–Liver axis; bacterial translocation; hepatic macrophages; PRRs; TLRs Axis for Treatment of Liver Fibrosis and Portal Hypertension.
    [Show full text]
  • Effects of Tributyrin Supplementation on Growth Performance, Insulin
    animals Article Effects of Tributyrin Supplementation on Growth Performance, Insulin, Blood Metabolites and Gut Microbiota in Weaned Piglets Stefania Sotira 1 , Matteo Dell’Anno 1,* , Valentina Caprarulo 1 , Monika Hejna 1, Federica Pirrone 2 , Maria Luisa Callegari 3 , Telma Vieira Tucci 4 and Luciana Rossi 1 1 Department of Health, Animal Science and Food Safety, Università degli Studi di Milano, via Trentacoste 2, 20134 Milan, Italy; [email protected] (S.S.); [email protected] (V.C.); [email protected] (M.H.); [email protected] (L.R.) 2 Department of Veterinary Medicine, Università degli Studi di Milano, Via dell’Università 6, 26900 Lodi, Italy; [email protected] 3 Department of Sustainable Food Process, Faculty of Agriculture, Food and Environmental Sciences, Università Cattolica del Sacro Cuore, via Emilia Parmense 84, 29122 Piacenza, Italy; [email protected] 4 Freelance Veterinarian, Via Fratelli Bandiera 28, 46100 Mantova, Italy; [email protected] * Correspondence: [email protected] Received: 28 February 2020; Accepted: 17 April 2020; Published: 22 April 2020 Simple Summary: In animal farming, alternatives to antibiotics are required due to the increase of antimicrobial resistance. In this contest, tributyrin showed the ability to promote gut health, to modulate gut microbiota and to improve protein digestibility, leading also to higher growth performance. However, although the mode of action of tributyrin on the intestinal epithelial cells has been partially explained, its effects on lipid and protein metabolism needs to be investigated. This paper provides information about the influence of tributyrin on production traits, blood parameters, faecal microbiota and faecal protein excretion in weaned piglets.
    [Show full text]
  • Design and Fabrication of Colloidal Delivery Systems to Encapsulate and Protect Curcumin: an Important Hydrophobic Nutraceutical
    University of Massachusetts Amherst ScholarWorks@UMass Amherst Doctoral Dissertations Dissertations and Theses July 2020 Design and Fabrication of Colloidal Delivery Systems to Encapsulate and Protect Curcumin: An Important Hydrophobic Nutraceutical Mahesh Kharat University of Massachusetts Amherst Follow this and additional works at: https://scholarworks.umass.edu/dissertations_2 Part of the Food Chemistry Commons Recommended Citation Kharat, Mahesh, "Design and Fabrication of Colloidal Delivery Systems to Encapsulate and Protect Curcumin: An Important Hydrophobic Nutraceutical" (2020). Doctoral Dissertations. 1930. https://doi.org/10.7275/17372938 https://scholarworks.umass.edu/dissertations_2/1930 This Open Access Dissertation is brought to you for free and open access by the Dissertations and Theses at ScholarWorks@UMass Amherst. It has been accepted for inclusion in Doctoral Dissertations by an authorized administrator of ScholarWorks@UMass Amherst. For more information, please contact [email protected]. DESIGN AND FABRICATION OF COLLOIDAL DELIVERY SYSTEMS TO ENCAPSULATE AND PROTECT CURCUMIN: AN IMPORTANT HYDROPHOBIC NUTRACEUTICAL A Dissertation Presented by MAHESH M. KHARAT Submitted to the Graduate School of the University of Massachusetts Amherst in partial fulfillment of the requirements for the degree of DOCTOR OF PHILOSOPHY May 2020 Food Science © Copyright by Mahesh M. Kharat 2020 All Rights Reserved DESIGN AND FABRICATION OF COLLOIDAL DELIVERY SYSTEMS TO ENCAPSULATE AND PROTECT CURCUMIN: AN IMPORTANT HYDROPHOBIC
    [Show full text]
  • Anticarcinogenic Actions of Tributyrin, a Butyric Acid Prodrug
    Send Orders of Reprints at [email protected] 1720 Current Drug Targets, 2012, 13, 1720-1729 Anticarcinogenic Actions of Tributyrin, A Butyric Acid Prodrug Renato Heidor, Juliana Festa Ortega, Aline de Conti, Thomas Prates Ong and Fernando Salvador Moreno* Laboratory of Diet, Nutrition and Cancer, Department of Food and Experimental Nutrition, Faculty of Pharmaceutical Sciences, University of São Paulo, Brazil Abstract: Bioactive food compounds (BFCs) exhibit potential anticarcinogenic effects that deserve to be explored. Bu- tyric acid (BA) is considered a promising BFC and has been used in clinical trials; however, its short half-life considera- bly restricts its therapeutic application. Tributyrin (TB), a BA prodrug present in milk fat and honey, has more favorable pharmacokinetic properties than BA, and its oral administration is also better tolerated. In vitro and in vivo studies have shown that TB acts on multiple anticancer cellular and molecular targets without affecting non-cancerous cells. Among the TB mechanisms of action, the induction of apoptosis and cell differentiation and the modulation of epigenetic mecha- nisms are notable. Due to its anticarcinogenic potential, strategies as lipid emulsions, nanoparticles, or structured lipids containing TB are currently being developed to improve its organoleptic characteristics and bioavailability. In addition, TB has minimal toxicity, making it an excellent candidate for combination therapy with other agents for the control of cancer. Despite the lack of data available in the literature, TB is a promising molecule for anticancer strategies. Therefore, additional preclinical and clinical studies should be performed using TB to elucidate its molecular targets and anticarcino- genic potential. Keywords: Bioactive food compounds, butyrate, butyric acid, cancer, cellular targets, chemoprevention, molecular targets, tributyrin.
    [Show full text]
  • Fecal Transplantation and Butyrate Improve Neuropathic Pain, Modify Immune Cell Profile, and Gene Expression in the PNS of Obese Mice
    Fecal transplantation and butyrate improve neuropathic pain, modify immune cell profile, and gene expression in the PNS of obese mice Raiza R. Bonomoa, Tyler M. Cooka, Chaitanya K. Gavinia, Chelsea R. Whitea, Jacob R. Jonesb, Elisa Bovoa, Aleksey V. Zimaa, Isabelle A. Browna, Lara R. Dugasc,d, Eleonora Zakharianb, Gregory Auberta,e, Francis Alonzo IIIf, Nigel A. Calcuttg, and Virginie Mansuy-Auberta,1 aDepartment of Cell and Molecular Physiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153; bDepartment of Cancer Biology and Pharmacology, University of Illinois College of Medicine, Peoria, IL 61605; cDepartment of Public Health Sciences, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153; dDepartment of Human Biology, University of Cape Town, Cape Town 7935, South Africa; eDepartment of Internal Medicine, Division of Cardiology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153; fDepartment of Microbiology and Immunology, Stritch School of Medicine, Loyola University Chicago, Maywood, IL 60153; and gDepartment of Pathology, University of California San Diego, La Jolla, CA 92093 Edited by Lawrence Steinman, Stanford University School of Medicine, Stanford, CA, and approved August 27, 2020 (received for review April 23, 2020) Obesity affects over 2 billion people worldwide and is accompa- nociceptors (13). Many previous studies have focused on hyper- nied by peripheral neuropathy (PN) and an associated poorer glycemia as the initiating insult in the development of prediabetic quality of life. Despite high prevalence, the molecular mechanisms and diabetic neuropathy, while a growing body of evidence has underlying the painful manifestations of PN are poorly under- also implicated dyslipidemia as a distinct pathogenic event (14–17).
    [Show full text]
  • Green Chemistry
    Green Chemistry Accepted Manuscript This is an Accepted Manuscript, which has been through the RSC Publishing peer review process and has been accepted for publication. Accepted Manuscripts are published online shortly after acceptance, which is prior Cutting-edge research for a greener sustainable future www.rsc.org/greenchem Volume 12 | Number 9 | September 2010 | Pages 1481–1676 to technical editing, formatting and proof reading. This free service from RSC Publishing allows authors to make their results available to the community, in citable form, before publication of the edited article. This Accepted Manuscript will be replaced by the edited and formatted Advance Article as soon as this is available. To cite this manuscript please use its permanent Digital Object Identifier (DOI®), which is identical for all formats of publication. More information about Accepted Manuscripts can be found in the Information for Authors. Please note that technical editing may introduce minor changes to the text and/or ISSN 1463-9262 COMMUNICATION CRITICAL REVIEW Luque, Varma and Baruwati Dumesic et al. graphics contained in the manuscript submitted by the author(s) which may alter Magnetically seperable organocatalyst Catalytic conversion of biomass for homocoupling of arylboronic acids to biofuels 1463-9262(2010)12:9;1-U content, and that the standard Terms & Conditions and the ethical guidelines that apply to the journal are still applicable. In no event shall the RSC be held responsible for any errors or omissions in these Accepted Manuscript manuscripts or any consequences arising from the use of any information contained in them. www.rsc.org/greenchem Registered Charity Number 207890 Page 1 of 26 Green Chemistry TABLE OF CONTENTS ENTRY Glycerol based solvents: synthesis, properties and applications José I.
    [Show full text]
  • Combined Index to USP 43 and NF 38, Volumes 1–5
    Combined Index to USP 43 and NF 38 Abaca-Acety I-1 Combined Index to USP 43 and NF 38, Volumes 1±5 Page citations refer to the pages of Volumes 1, 2, 3, 4 and 5 of USP 43±NF 38. This index is repeated in its entirety in each volume. 1±2482 Volume 1 2483±4722 Volume 2 4723±6108 Volume 3 6109±7208 Volume 4 7209±8760 Volume 5 Numbers in angle brackets such as 〈421〉 refer to chapter numbers in the General Chapters section. and (salts of) chlorpheniramine, and tramadol hydrochloride oral A dextromethorphan, and suspension, 4452 pseudoephedrine, capsules containing at Acetanilide, 6132 Abacavir least three of the following, 52 Acetate oral solution, 19 and (salts of) chlorpheniramine, methyl, 6178 sulfate, 23 dextromethorphan, and Acetate buffer, 6145 tablets, 20 pseudoephedrine, oral powder TS, 6225 and lamivudine tablets, 21 containing at least three of the Acetazolamide, 73 Abiraterone following, 54 for injection, 74 acetate, 25 and (salts of) chlorpheniramine, oral suspension, 76 acetate tablets, 26 dextromethorphan, and tablets, 76 Absolute pseudoephedrine, oral solution Acetic acid, 5599, 6132 alcohol, 6133 containing at least three of the ammonium acetate buffer TS, 6225 ether, 6131 following, 56 diluted, 5599, 6132, 6159 Absorbable and (salts of) chlorpheniramine, double-normal (2 N), 6238 dusting powder, 1569 dextromethorphan, and glacial, 77, 6132, 6168 gelatin film, 2092 pseudoephedrine, tablets containing at glacial, TS, 6229 gelatin sponge, 2093 least three of the following, 58 and hydrocortisone otic solution, 2235 surgical suture,
    [Show full text]
  • Metabolomics Identifies a Biomarker Revealing in Vivo Loss of Functional ß-Cell Mass
    Page 1 of 46 Diabetes Metabolomics identifies a biomarker revealing in vivo loss of functional ß-cell mass before diabetes onset Lingzi Li1,2,7, Petra Krznar3,4,7, Alexander Erban5, Andrea Agazzi6, Juliette Martin-Levilain1,2, Sachin Supale1,2, Joachim Kopka5, Nicola Zamboni3 and Pierre Maechler1,2 1Department of Cell Physiology and Metabolism & 2Faculty Diabetes Centre, University of Geneva Medical Centre, Geneva, Switzerland 3Institute of Molecular Systems Biology, ETH Zurich, Zurich, Switzerland 4PhD Program Systems Biology, Life Science Zurich Graduate School, Zurich, Switzerland 5Max Planck Institute of Molecular Plant Physiology, 14476 Potsdam, Germany. 6Theoretical Physics Department, University of Geneva, Geneva, Switzerland 7These authors contributed equally to this work Correspondence to: Pierre Maechler, Department of Cell Physiology, University of Geneva Medical Center, rue Michel- Servet 1, 1211 Geneva 4, Switzerland. Email: [email protected] , Phone: +41 22 379 55 54. Nicola Zamboni, Institute of Molecular Systems Biology, ETH Zurich, Otto-Stern-Weg 3, 8093 Zürich, Switzerland. Email: [email protected] , Phone: +41 44 633 31 41. Keywords: pre-diabetes; beta-cell; biomarker; 1,5-anhydroglucitol Running title: biomarkers of beta-cell loss Word count: 5’246 1 Diabetes Publish Ahead of Print, published online September 19, 2019 Diabetes Page 2 of 46 ABSTRACT Identification of pre-diabetic individuals with decreased functional ß-cell mass is essential for the prevention of diabetes. However, in vivo detection of early asymptomatic ß-cell defect remains unsuccessful. Metabolomics emerged as a powerful tool in providing read-outs of early disease states before clinical manifestation. We aimed at identifying novel plasma biomarkers for loss of functional ß-cell mass in the asymptomatic pre-diabetic stage.
    [Show full text]