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Elevated circulating follistatin associates with an increased risk of type 2 diabetes.
Wu, Chuanyan; Borné, Yan; Gao, Rui; López Rodriguez, Maykel; Roell, William C; Wilson, Jonathan M; Regmi, Ajit; Luan, Cheng; Aly, Dina Mansour; Peter, Andreas; Machann, Jürgen; Staiger, Harald; Fritsche, Andreas; Birkenfeld, Andreas L; Tao, Rongya; Wagner, Robert; Canouil, Mickaël; Hong, Mun-Gwan; Schwenk, Jochen M; Ahlqvist, Emma; Kaikkonen, Minna U; Nilsson, Peter; Shore, Angela C; Khan, Faisel; Natali, Andrea; Melander, Olle; Orho-Melander, Marju; Nilsson, Jan; Häring, Hans-Ulrich; Renström, Erik; Wollheim, Claes B; Engström, Gunnar; Weng, Jianping; Pearson, Ewan R; Franks, Paul W; White, Morris F; Duffin, Kevin L; Vaag, Allan Arthur; Laakso, Markku; Stefan, Norbert; Groop, Leif; De Marinis, Yang.
Afiliação
  • Wu C; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Borné Y; School of Control Science and Engineering, Shandong University, Jinan, Shandong, China.
  • Gao R; School of Intelligent Engineering, Shandong Management University, Jinan, Shandong, China.
  • López Rodriguez M; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Roell WC; School of Control Science and Engineering, Shandong University, Jinan, Shandong, China.
  • Wilson JM; Institute of Clinical Medicine, Internal Medicine, University of Eastern Finland, Kuopio, Finland.
  • Regmi A; A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, Kuopio, Finland.
  • Luan C; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
  • Aly DM; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
  • Peter A; Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, IN, USA.
  • Machann J; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Staiger H; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Fritsche A; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology; and Department for Diagnostic Laboratory Medicine, Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tübingen, University of Tübingen, Tübingen, Germany.
  • Birkenfeld AL; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich, Tübingen, Germany.
  • Tao R; German Center for Diabetes Research (DZD), Tübingen, Germany.
  • Wagner R; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich, Tübingen, Germany.
  • Canouil M; German Center for Diabetes Research (DZD), Tübingen, Germany.
  • Hong MG; Section of Experimental Radiology, Department of Radiology, University of Tübingen, Tübingen, Germany.
  • Schwenk JM; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology; and Department for Diagnostic Laboratory Medicine, Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tübingen, University of Tübingen, Tübingen, Germany.
  • Ahlqvist E; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich, Tübingen, Germany.
  • Kaikkonen MU; German Center for Diabetes Research (DZD), Tübingen, Germany.
  • Nilsson P; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology; and Department for Diagnostic Laboratory Medicine, Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tübingen, University of Tübingen, Tübingen, Germany.
  • Shore AC; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich, Tübingen, Germany.
  • Khan F; German Center for Diabetes Research (DZD), Tübingen, Germany.
  • Natali A; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology; and Department for Diagnostic Laboratory Medicine, Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tübingen, University of Tübingen, Tübingen, Germany.
  • Melander O; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich, Tübingen, Germany.
  • Orho-Melander M; German Center for Diabetes Research (DZD), Tübingen, Germany.
  • Nilsson J; Division of Endocrinology, Boston Children's Hospital, Harvard Medical School, Boston, MA, USA.
  • Häring HU; Department of Internal Medicine IV, Division of Endocrinology, Diabetology and Nephrology; and Department for Diagnostic Laboratory Medicine, Institute for Clinical Chemistry and Pathobiochemistry, University Hospital Tübingen, University of Tübingen, Tübingen, Germany.
  • Renström E; Institute of Diabetes Research and Metabolic Diseases (IDM) of the Helmholtz Center Munich, Tübingen, Germany.
  • Wollheim CB; German Center for Diabetes Research (DZD), Tübingen, Germany.
  • Engström G; Inserm U1283 / CNRS UMR 8199, European Genomic Institute for Diabetes (EGID), Institut Pasteur de Lille; University of Lille, Lille University Hospital, Lille, France.
  • Weng J; Affinity Proteomics, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Pearson ER; Affinity Proteomics, Science for Life Laboratory, KTH Royal Institute of Technology, Stockholm, Sweden.
  • Franks PW; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • White MF; A.I. Virtanen Institute for Molecular Sciences, Department of Biotechnology and Molecular Medicine, University of Eastern Finland, Kuopio, Finland.
  • Duffin KL; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • Vaag AA; NIHR Exeter Clinical Research Facility, Royal Devon and Exeter Hospital and University of Exeter Medical School, Exeter, Devon, UK.
  • Laakso M; Division of Systems Medicine, University of Dundee, Ninewells Hospital & Medical School, Dundee, UK.
  • Stefan N; Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy.
  • Groop L; Department of Clinical Sciences, Lund University, Malmö, Sweden.
  • De Marinis Y; Department of Clinical Sciences, Lund University, Malmö, Sweden.
Nat Commun ; 12(1): 6486, 2021 11 10.
Article em En | MEDLINE | ID: mdl-34759311
ABSTRACT
The hepatokine follistatin is elevated in patients with type 2 diabetes (T2D) and promotes hyperglycemia in mice. Here we explore the relationship of plasma follistatin levels with incident T2D and mechanisms involved. Adjusted hazard ratio (HR) per standard deviation (SD) increase in follistatin levels for T2D is 1.24 (CI 1.04-1.47, p < 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI 1.09-1.58, p < 0.01) during 4-year follow-up (n = 883, Finland). High circulating follistatin associates with adipose tissue insulin resistance and non-alcoholic fatty liver disease (n = 210, Germany). In human adipocytes, follistatin dose-dependently increases free fatty acid release. In genome-wide association study (GWAS), variation in the glucokinase regulatory protein gene (GCKR) associates with plasma follistatin levels (n = 4239, Sweden; n = 885, UK, Italy and Sweden) and GCKR regulates follistatin secretion in hepatocytes in vitro. Our findings suggest that GCKR regulates follistatin secretion and that elevated circulating follistatin associates with an increased risk of T2D by inducing adipose tissue insulin resistance.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Folistatina / Diabetes Mellitus Tipo 2 Tipo de estudo: Etiology_studies / Risk_factors_studies Limite: Humans / Middle aged Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Suécia
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Folistatina / Diabetes Mellitus Tipo 2 Tipo de estudo: Etiology_studies / Risk_factors_studies Limite: Humans / Middle aged Idioma: En Revista: Nat Commun Assunto da revista: BIOLOGIA / CIENCIA Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Suécia