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J-GLOBAL ID：201702251188956434   整理番号：17A0363092

グルカゴンおよび甲状腺ホルモンの化学的ハイブリダイゼーションは代謝性疾患に対する治療的影響を最適化する【Powered by NICT】

Chemical Hybridization of Glucagon and Thyroid Hormone Optimizes Therapeutic Impact for Metabolic Disease

著者 (70件)： Finan Brian (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Finan Brian (Division of Metabolic Diseases, Department of Medicine, Technische Universitaet Muenchen, 80333 Munich, Germany) ,  Finan Brian (German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany) ,  Clemmensen Christoffer (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Clemmensen Christoffer (Division of Metabolic Diseases, Department of Medicine, Technische Universitaet Muenchen, 80333 Munich, Germany) ,  Clemmensen Christoffer (German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany) ,  Zhu Zhimeng (Department of Chemistry, Indiana University, Bloomington, IN 47405, USA) ,  Stemmer Kerstin (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Stemmer Kerstin (Division of Metabolic Diseases, Department of Medicine, Technische Universitaet Muenchen, 80333 Munich, Germany) ,  Stemmer Kerstin (German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany) ,  Gauthier Karine (Institut de Genomique Fonctionnelle de Lyon, Universite de Lyon, Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA), Ecole Normale Superieure de Lyon, 69364 Lyon, France) ,  Mueller Luisa (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  De Angelis Meri (Molecular EXposomics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Moreth Kristin (German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany) ,  Neff Frauke (German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany) ,  Neff Frauke (Institute of Pathology, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany) ,  Perez-Tilve Diego (Division of Endocrinology, Department of Internal Medicine, Metabolic Diseases Institute, University of Cincinnati College of Medicine, Cincinnati, OH 45237, USA) ,  Fischer Katrin (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Fischer Katrin (Division of Metabolic Diseases, Department of Medicine, Technische Universitaet Muenchen, 80333 Munich, Germany) ,  Lutter Dominik (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Lutter Dominik (Division of Metabolic Diseases, Department of Medicine, Technische Universitaet Muenchen, 80333 Munich, Germany) ,  Lutter Dominik (German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany) ,  Sanchez-Garrido Miguel A. (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Sanchez-Garrido Miguel A. (Division of Metabolic Diseases, Department of Medicine, Technische Universitaet Muenchen, 80333 Munich, Germany) ,  Liu Peng (Institute of Comparative Molecular Endocrinology, University of Ulm, 89081 Ulm, Germany) ,  Tuckermann Jan (Institute of Comparative Molecular Endocrinology, University of Ulm, 89081 Ulm, Germany) ,  Malehmir Mohsen (Department of Pathology and Molecular Pathology, University Zurich and University Hospital Zurich, 8091 Zurich, Switzerland) ,  Healy Marc E. (Department of Pathology and Molecular Pathology, University Zurich and University Hospital Zurich, 8091 Zurich, Switzerland) ,  Weber Achim (Department of Pathology and Molecular Pathology, University Zurich and University Hospital Zurich, 8091 Zurich, Switzerland) ,  Heikenwalder Mathias (Institute of Virology, Technische Universitaet Muenchen, 81675 Munich, Germany) ,  Heikenwalder Mathias (Division of Chronic Inflammation and Cancer, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany) ,  Jastroch Martin (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Jastroch Martin (Division of Metabolic Diseases, Department of Medicine, Technische Universitaet Muenchen, 80333 Munich, Germany) ,  Kleinert Maximilian (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Kleinert Maximilian (Division of Metabolic Diseases, Department of Medicine, Technische Universitaet Muenchen, 80333 Munich, Germany) ,  Kleinert Maximilian (Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, 2200 Copenhagen, Denmark) ,  Jall Sigrid (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Jall Sigrid (Division of Metabolic Diseases, Department of Medicine, Technische Universitaet Muenchen, 80333 Munich, Germany) ,  Brandt Sara (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Brandt Sara (Division of Metabolic Diseases, Department of Medicine, Technische Universitaet Muenchen, 80333 Munich, Germany) ,  Flamant Frederic (Institut de Genomique Fonctionnelle de Lyon, Universite de Lyon, Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA), Ecole Normale Superieure de Lyon, 69364 Lyon, France) ,  Schramm Karl-Werner (Molecular EXposomics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Biebermann Heike (Institute of Experimental Pediatric Endocrinology, Charite-Universitaetsmedizin Berlin, Berlin 13353, Germany) ,  Doring Yvonne (Department of Medicine, Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universitaet Muenchen, 80336, Munich, Germany) ,  Doring Yvonne (German Centre for Cardiovascular Research (DZHK), partner site Munich Heart Alliance (MHA), 80336 Munich, Germany) ,  Weber Christian (Department of Medicine, Institute for Cardiovascular Prevention, Ludwig-Maximilians-Universitaet Muenchen, 80336, Munich, Germany) ,  Weber Christian (Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, 6200 MD Maastricht, The Netherlands) ,  Habegger Kirk M. (Comprehensive Diabetes Center and Department of Medicine-Endocrinology, Diabetes & Metabolism, University of Alabama at Birmingham, Birmingham, AL 35294, USA) ,  Keuper Michaela (Institute for Diabetes and Regeneration, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg 85764, Germany) ,  Gelfanov Vasily (Department of Chemistry, Indiana University, Bloomington, IN 47405, USA) ,  Liu Fa (Calibrium LLC, Carmel, IN 46032, USA) ,  Kohrle Josef (Institute for Experimental Endocrinology, Charite-Universitaetsmedizin Berlin, Berlin 13353, Germany) ,  Rozman Jan (German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany) ,  Rozman Jan (German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany) ,  Fuchs Helmut (German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany) ,  Gailus-Durner Valerie (German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany) ,  Hrabe de Angelis Martin (German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany) ,  Hrabe de Angelis Martin (German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum Muenchen, German Research Center for Environmental Health, 85764 Neuherberg, Germany) ,  Hrabe de Angelis Martin (Chair of Experimental Genetics, School of Life Science Weihenstephan, Technische Universitaet Muenchen, Freising 85353, Germany) ,  Hofmann Susanna M. (German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany) ,  Hofmann Susanna M. (Institute for Diabetes and Regeneration, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), Neuherberg 85764, Germany) ,  Hofmann Susanna M. (Medizinische Klinik und Poliklinik IV, Klinikum der LMU, Muenchen 80336, Germany) ,  Yang Bin (Department of Chemistry, Indiana University, Bloomington, IN 47405, USA) ,  Tschop Matthias H. (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Tschop Matthias H. (Division of Metabolic Diseases, Department of Medicine, Technische Universitaet Muenchen, 80333 Munich, Germany) ,  Tschop Matthias H. (German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany) ,  DiMarchi Richard (Department of Chemistry, Indiana University, Bloomington, IN 47405, USA) ,  Mueller Timo D. (Institute for Diabetes and Obesity, Helmholtz Diabetes Center at Helmholtz Zentrum Muenchen, German Research Center for Environmental Health (GmbH), 85764 Neuherberg, Germany) ,  Mueller Timo D. (Division of Metabolic Diseases, Department of Medicine, Technische Universitaet Muenchen, 80333 Munich, Germany) ,  Mueller Timo D. (German Center for Diabetes Research (DZD), 85764 Neuherberg, Germany)
資料名： Cell (Cambridge, Mass.)  (Cell (Cambridge, Mass.))
巻： 167  号： 3  ページ： 843-857.e14  発行年： 2016年 
JST資料番号： A0707B  ISSN： 0092-8674  資料種別： 逐次刊行物 (A)
記事区分： 原著論文  発行国： アメリカ合衆国 (USA)  言語： 英語 (EN)

抄録/ポイント： グルカゴンおよび甲状腺ホルモン(T_3)は,代謝性疾患に対する治療の可能性を示すが,望ましくない効果を示した。はこれら二種のホルモンの相乗効果と一正確に標的分子内の両活性のデリバリーを可能にする工学化学複合体によるそれらの悪影響の軽減を達成した。配位グルカゴンおよびT_3作用は代謝的に損なわれたマウスにおける高脂血症,脂肪性肝炎,アテローム性動脈硬化症,耐糖能異常,肥満を補正するために相乗的に作用する。各ホルモン成分は相互に強化された肝臓のコレステロール代謝と白色脂肪褐色化を介して肝細胞と脂肪細胞の細胞過程を高めることを示した。グルカゴンとT_3により駆動される同期シグナル伝達は相互に各ホルモンの固有の有害な影響を最小化する。肝臓指向T_3作用オフセットグルカゴンの糖尿病誘発責任と,グルカゴン仲介デリバリーは有害T_3作用から心血管系では使わなかった。著者らの知見は,肥満2型糖尿病,心血管疾患の治療のためのユニークな可能性を提供することを単一分子実体にこれらのホルモンを統合することの治療的有用性を支持した。Copyright 2017 Elsevier B.V., Amsterdam. All rights reserved. Translated from English into Japanese by JST.【Powered by NICT】

シソーラス用語： *最適化 ,  アテローム性動脈硬化症 ,  *ホルモン ,  肥満 ,  肝細胞 ,  *代謝 ,  *代謝性疾患 ,  相乗作用 ,  *グルカゴン ,  薬理学 ,  脂肪細胞 ,  *甲状腺ホルモン ,  糖尿病 ,  コレステロール代謝 ,  標的分子 ,  *改変

著者キーワード (8件)： グルカゴン ,  甲状腺ホルモン ,  複合体 ,  Co agonist ,  肥満 ,  脂質異常症 ,  NASH ,  多薬理学

分類 (2件)： 遺伝子発現  (EC02040Q) ,  生物学的機能  (EB03040U)

タイトルに関連する用語 (7件)： グルカゴン ,  甲状腺ホルモン ,  化学 ,  ハイブリダイゼーション ,  代謝性疾患 ,  治療 ,  最適化