The browser you are using is not supported by this website. All versions of Internet Explorer are no longer supported, either by us or Microsoft (read more here: https://www.microsoft.com/en-us/microsoft-365/windows/end-of-ie-support).

Please use a modern browser to fully experience our website, such as the newest versions of Edge, Chrome, Firefox or Safari etc.

Default user image.

Cheng Luan

Research engineer

Default user image.

Elevated circulating follistatin associates with an increased risk of type 2 diabetes

Author

  • Chuanyan Wu
  • Yan Borné
  • Rui Gao
  • Maykel López Rodriguez
  • William C Roell
  • Jonathan M Wilson
  • Ajit Regmi
  • Cheng Luan
  • Dina Mansour Aly
  • Andreas Peter
  • Jürgen Machann
  • Harald Staiger
  • Andreas Fritsche
  • Andreas L Birkenfeld
  • Rongya Tao
  • Robert Wagner
  • Mickaël Canouil
  • Mun-Gwan Hong
  • Jochen M Schwenk
  • Emma Ahlqvist
  • Minna U Kaikkonen
  • Peter Nilsson
  • Angela C Shore
  • Faisel Khan
  • Andrea Natali
  • Olle Melander
  • Marju Orho-Melander
  • Jan Nilsson
  • Hans-Ulrich Häring
  • Erik Renström
  • Claes B Wollheim
  • Gunnar Engström
  • Jianping Weng
  • Ewan R Pearson
  • Paul W Franks
  • Morris F White
  • Kevin L Duffin
  • Allan Arthur Vaag
  • Markku Laakso
  • Norbert Stefan
  • Leif Groop
  • Yang De Marinis

Summary, in English

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.

Department/s

  • Genomics, Diabetes and Endocrinology
  • EXODIAB: Excellence of Diabetes Research in Sweden
  • Nutrition Epidemiology
  • EpiHealth: Epidemiology for Health
  • Diabetes - Islet Patophysiology
  • Internal Medicine - Epidemiology
  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Diabetic Complications
  • Cardiovascular Research - Epidemiology
  • Genetic and Molecular Epidemiology

Publishing year

2021

Language

English

Pages

1-10

Publication/Series

Nature Communications

Volume

12

Document type

Journal article

Publisher

Nature Publishing Group

Topic

  • Endocrinology and Diabetes

Status

Published

Research group

  • Genomics, Diabetes and Endocrinology
  • Nutrition Epidemiology
  • Diabetes - Islet Patophysiology
  • Internal Medicine - Epidemiology
  • Cardiovascular Research - Hypertension
  • Diabetes - Cardiovascular Disease
  • Cardiovascular Research - Immunity and Atherosclerosis
  • Diabetic Complications
  • Cardiovascular Research - Epidemiology
  • Genetic and Molecular Epidemiology

ISBN/ISSN/Other

  • ISSN: 2041-1723