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Genome-wide association study and functional characterization identifies candidate genes for insulin-stimulated glucose uptake.
Williamson, Alice; Norris, Dougall M; Yin, Xianyong; Broadaway, K Alaine; Moxley, Anne H; Vadlamudi, Swarooparani; Wilson, Emma P; Jackson, Anne U; Ahuja, Vasudha; Andersen, Mette K; Arzumanyan, Zorayr; Bonnycastle, Lori L; Bornstein, Stefan R; Bretschneider, Maxi P; Buchanan, Thomas A; Chang, Yi-Cheng; Chuang, Lee-Ming; Chung, Ren-Hua; Clausen, Tine D; Damm, Peter; Delgado, Graciela E; de Mello, Vanessa D; Dupuis, Josée; Dwivedi, Om P; Erdos, Michael R; Fernandes Silva, Lilian; Frayling, Timothy M; Gieger, Christian; Goodarzi, Mark O; Guo, Xiuqing; Gustafsson, Stefan; Hakaste, Liisa; Hammar, Ulf; Hatem, Gad; Herrmann, Sandra; Højlund, Kurt; Horn, Katrin; Hsueh, Willa A; Hung, Yi-Jen; Hwu, Chii-Min; Jonsson, Anna; Kårhus, Line L; Kleber, Marcus E; Kovacs, Peter; Lakka, Timo A; Lauzon, Marie; Lee, I-Te; Lindgren, Cecilia M; Lindström, Jaana; Linneberg, Allan.
Afiliação
  • Williamson A; MRC Epidemiology Unit Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, UK.
  • Norris DM; Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science, Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK.
  • Yin X; Metabolic Research Laboratories Wellcome Trust-MRC Institute of Metabolic Science, Department of Clinical Biochemistry, University of Cambridge, Cambridge, UK.
  • Broadaway KA; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
  • Moxley AH; Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Vadlamudi S; Department of Epidemiology, School of Public Health, Nanjing Medical University, Nanjing, China.
  • Wilson EP; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
  • Jackson AU; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
  • Ahuja V; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
  • Andersen MK; Department of Genetics, University of North Carolina, Chapel Hill, NC, USA.
  • Arzumanyan Z; Department of Biostatistics, University of Michigan, Ann Arbor, MI, USA.
  • Bonnycastle LL; Center for Statistical Genetics, University of Michigan, Ann Arbor, MI, USA.
  • Bornstein SR; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Bretschneider MP; Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Buchanan TA; Department of Pediatrics, Genomic Outcomes, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Chang YC; Center for Precision Health Research National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Chuang LM; Department of Internal Medicine III, Metabolic and Vascular Medicine, Medical Faculty Carl Gustav Carus, Dresden, Germany.
  • Chung RH; Helmholtz Zentrum München Paul Langerhans Institute Dresden (PLID), University Hospital and Faculty of Medicine TU Dresden, Dresden, Germany.
  • Clausen TD; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
  • Damm P; Department of Internal Medicine III, Metabolic and Vascular Medicine, Medical Faculty Carl Gustav Carus, Dresden, Germany.
  • Delgado GE; Helmholtz Zentrum München Paul Langerhans Institute Dresden (PLID), University Hospital and Faculty of Medicine TU Dresden, Dresden, Germany.
  • de Mello VD; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
  • Dupuis J; Department of Medicine, Division of Endocrinology and Diabetes, Keck School of Medicine USC, Los Angeles, CA, USA.
  • Dwivedi OP; Graduate Institute of Medical Genomics and Proteomics, National Taiwan University, Taipei City, Taiwan.
  • Erdos MR; Internal Medicine, National Taiwan University Hospital, Taipei City, Taiwan.
  • Fernandes Silva L; Institute of Biomedical Sciences, Academia Sinica, Taipei City, Taiwan.
  • Frayling TM; Department of Internal Medicine, Division of Endocrinology and Metabolism, National Taiwan University Hospital, Taipei City, Taiwan.
  • Gieger C; Institute of Population Health Sciences, National Health Research Institutes, Toufen, Taiwan.
  • Goodarzi MO; Department of Gynecology and Obstetrics, Nordsjaellands Hospital, Hillerød, Denmark.
  • Guo X; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Gustafsson S; Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
  • Hakaste L; Center for Pregnant Women with Diabetes, Rigshospitalet, Copenhagen, Denmark.
  • Hammar U; Department of Obstetrics, Rigshospitalet, Copenhagen, Denmark.
  • Hatem G; Vth Department of Medicine, Medical Faculty Mannheim, Heidelberg University, Mannheim, Germany.
  • Herrmann S; Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
  • Højlund K; Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.
  • Horn K; Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montréal, Quebec, Canada.
  • Hsueh WA; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Hung YJ; Center for Precision Health Research National Human Genome Research Institute, National Institutes of Health, Bethesda, MD, USA.
  • Hwu CM; Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland.
  • Jonsson A; University of Exeter Medical School University of Exeter, Exeter, UK.
  • Kårhus LL; German Center for Diabetes Research (DZD e.V.), Neuherberg, Germany.
  • Kleber ME; Institute of Epidemiology II, Helmholtz Zentrum München-German Research Center for Environmental Health, Neuherberg, Germany.
  • Kovacs P; Department of Medicine, Division of Endocrinology, Diabetes and Metabolism Cedars-Sinai Medical Center, Los Angeles, CA, USA.
  • Lakka TA; Department of Pediatrics, Genomic Outcomes, The Institute for Translational Genomics and Population Sciences, The Lundquist Institute for Biomedical Innovation at Harbor-UCLA Medical Center, Torrance, CA, USA.
  • Lauzon M; Department of Medical Sciences, Clinical Epidemiology, Uppsala University, Uppsala, Sweden.
  • Lee IT; Institute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki, Finland.
  • Lindgren CM; Department of Medical Sciences, Molecular Epidemiology, Uppsala University, Uppsala, Sweden.
  • Lindström J; Clinical Sciences Malmö, Genomics, Diabetes and Endocrinology, Lund University, Malmö, Sweden.
  • Linneberg A; Helmholtz Zentrum München Paul Langerhans Institute Dresden (PLID), University Hospital and Faculty of Medicine TU Dresden, Dresden, Germany.
Nat Genet ; 55(6): 973-983, 2023 06.
Article em En | MEDLINE | ID: mdl-37291194
ABSTRACT
Distinct tissue-specific mechanisms mediate insulin action in fasting and postprandial states. Previous genetic studies have largely focused on insulin resistance in the fasting state, where hepatic insulin action dominates. Here we studied genetic variants influencing insulin levels measured 2 h after a glucose challenge in >55,000 participants from three ancestry groups. We identified ten new loci (P < 5 × 10-8) not previously associated with postchallenge insulin resistance, eight of which were shown to share their genetic architecture with type 2 diabetes in colocalization analyses. We investigated candidate genes at a subset of associated loci in cultured cells and identified nine candidate genes newly implicated in the expression or trafficking of GLUT4, the key glucose transporter in postprandial glucose uptake in muscle and fat. By focusing on postprandial insulin resistance, we highlighted the mechanisms of action at type 2 diabetes loci that are not adequately captured by studies of fasting glycemic traits.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Resistência à Insulina / Diabetes Mellitus Tipo 2 Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
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XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Resistência à Insulina / Diabetes Mellitus Tipo 2 Tipo de estudo: Risk_factors_studies Limite: Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article