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

Wu, Chuanyan LU ; Borné, Yan LU ; Gao, Rui ; López Rodriguez, Maykel ; Roell, William C ; Wilson, Jonathan M ; Regmi, Ajit ; Luan, Cheng LU ; Aly, Dina Mansour LU and Peter, Andreas , et al. (2021) In Nature Communications 12. p.1-10
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),... (More)

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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Nature Communications
volume
12
article number
6486
pages
1 - 10
publisher
Nature Publishing Group
external identifiers
  • pmid:34759311
  • scopus:85118927999
ISSN
2041-1723
DOI
10.1038/s41467-021-26536-w
language
English
LU publication?
yes
additional info
© 2021. The Author(s).
id
3ffb542e-fb4d-4c5e-a905-9d4b765a4570
date added to LUP
2021-11-26 13:53:27
date last changed
2024-04-20 17:34:56
@article{3ffb542e-fb4d-4c5e-a905-9d4b765a4570,
  abstract     = {{<p>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 &lt; 0.05) during 19-year follow-up (n = 4060, Sweden); and 1.31 (CI: 1.09-1.58, p &lt; 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.</p>}},
  author       = {{Wu, Chuanyan and Borné, Yan and Gao, Rui and López Rodriguez, Maykel and Roell, William C and Wilson, Jonathan M and Regmi, Ajit and Luan, Cheng and Aly, Dina Mansour and Peter, Andreas and Machann, Jürgen and Staiger, Harald and Fritsche, Andreas and Birkenfeld, Andreas L and Tao, Rongya and Wagner, Robert and Canouil, Mickaël and Hong, Mun-Gwan and Schwenk, Jochen M and Ahlqvist, Emma and Kaikkonen, Minna U and Nilsson, Peter and Shore, Angela C and Khan, Faisel and Natali, Andrea and Melander, Olle and Orho-Melander, Marju and Nilsson, Jan and Häring, Hans-Ulrich and Renström, Erik and Wollheim, Claes B and Engström, Gunnar and Weng, Jianping and Pearson, Ewan R and Franks, Paul W and White, Morris F and Duffin, Kevin L and Vaag, Allan Arthur and Laakso, Markku and Stefan, Norbert and Groop, Leif and De Marinis, Yang}},
  issn         = {{2041-1723}},
  language     = {{eng}},
  pages        = {{1--10}},
  publisher    = {{Nature Publishing Group}},
  series       = {{Nature Communications}},
  title        = {{Elevated circulating follistatin associates with an increased risk of type 2 diabetes}},
  url          = {{http://dx.doi.org/10.1038/s41467-021-26536-w}},
  doi          = {{10.1038/s41467-021-26536-w}},
  volume       = {{12}},
  year         = {{2021}},
}