Circulating follistatin and activin A and their regulation by insulin in obesity and type 2 diabetes

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Standard

Circulating follistatin and activin A and their regulation by insulin in obesity and type 2 diabetes. / Sylow, Lykke; Vind, Birgitte F; Kruse, Rikke; Møller, Pauline M; Wojtaszewski, Jørgen; Richter, Erik A.; Højlund, Kurt.

I: Journal of Clinical Endocrinology and Metabolism, Bind 105, Nr. 5, 2020, s. 1343-1354.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Sylow, L, Vind, BF, Kruse, R, Møller, PM, Wojtaszewski, J, Richter, EA & Højlund, K 2020, 'Circulating follistatin and activin A and their regulation by insulin in obesity and type 2 diabetes', Journal of Clinical Endocrinology and Metabolism, bind 105, nr. 5, s. 1343-1354. https://doi.org/10.1210/clinem/dgaa090

APA

Sylow, L., Vind, B. F., Kruse, R., Møller, P. M., Wojtaszewski, J., Richter, E. A., & Højlund, K. (2020). Circulating follistatin and activin A and their regulation by insulin in obesity and type 2 diabetes. Journal of Clinical Endocrinology and Metabolism, 105(5), 1343-1354. https://doi.org/10.1210/clinem/dgaa090

Vancouver

Sylow L, Vind BF, Kruse R, Møller PM, Wojtaszewski J, Richter EA o.a. Circulating follistatin and activin A and their regulation by insulin in obesity and type 2 diabetes. Journal of Clinical Endocrinology and Metabolism. 2020;105(5):1343-1354. https://doi.org/10.1210/clinem/dgaa090

Author

Sylow, Lykke ; Vind, Birgitte F ; Kruse, Rikke ; Møller, Pauline M ; Wojtaszewski, Jørgen ; Richter, Erik A. ; Højlund, Kurt. / Circulating follistatin and activin A and their regulation by insulin in obesity and type 2 diabetes. I: Journal of Clinical Endocrinology and Metabolism. 2020 ; Bind 105, Nr. 5. s. 1343-1354.

Bibtex

@article{b059512eb9c749a88064c84e9a60a9b0,
title = "Circulating follistatin and activin A and their regulation by insulin in obesity and type 2 diabetes",
abstract = "Background: Circulating follistatin (Fst) binds activin A and thereby regulates biological functions such as muscle growth and β-cell survival. However, Fst and activin A's implication in metabolic regulation is unclear.Objective: To investigate circulating Fst and activin A in obesity and type 2 diabetes (T2D) and determine their association with metabolic parameters. Further, to examine regulation of Fst and activin A by insulin and the influence of obesity and T2D hereon.Methods: Plasma Fst and activin A levels were analyzed in obese T2D patients (N=10) closely matched to glucose-tolerant lean (N=12) and obese (N=10) individuals in the fasted state and following a 4-hour hyperinsulinemic-euglycemic clamp (40 mU·m-2·min-1) combined with indirect calorimetry.Results: Circulating Fst was ~30{\%} higher in patients with T2D compared with both lean and obese non-diabetic individuals (P <0.001), while plasma activin A was unaltered. In the total cohort, fasting plasma Fst correlated positively with fasting plasma glucose, serum insulin and C-peptide levels, HOMA2-IR, hepatic and adipose tissue insulin resistance after adjusting for age, gender and group (all r >0.47; P <0.05). However, in the individual groups these correlations only achieved significance in patients with T2D (not plasma glucose). Acute hyperinsulinemia at euglycemia reduced circulating Fst by ~30{\%} (P <0.001) and this response was intact in patients with T2D. Insulin inhibited FST expression in human hepatocytes after 2-hours and even further after 48-hours.Conclusions: Elevated circulating Fst, but not activin A, is strongly associated with measures of insulin resistance in patients with T2D. However, the ability of insulin to suppress circulating Fst is preserved in T2D.",
keywords = "Faculty of Science, Follistatin, Activin A, Insulin resistance, Insulin, Type 2 diabetes",
author = "Lykke Sylow and Vind, {Birgitte F} and Rikke Kruse and M{\o}ller, {Pauline M} and J{\o}rgen Wojtaszewski and Richter, {Erik A.} and Kurt H{\o}jlund",
note = "{\circledC} Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.",
year = "2020",
doi = "10.1210/clinem/dgaa090",
language = "English",
volume = "105",
pages = "1343--1354",
journal = "Journal of Clinical Endocrinology and Metabolism",
issn = "0021-972X",
publisher = "Oxford University Press",
number = "5",

}

RIS

TY - JOUR

T1 - Circulating follistatin and activin A and their regulation by insulin in obesity and type 2 diabetes

AU - Sylow, Lykke

AU - Vind, Birgitte F

AU - Kruse, Rikke

AU - Møller, Pauline M

AU - Wojtaszewski, Jørgen

AU - Richter, Erik A.

AU - Højlund, Kurt

N1 - © Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

PY - 2020

Y1 - 2020

N2 - Background: Circulating follistatin (Fst) binds activin A and thereby regulates biological functions such as muscle growth and β-cell survival. However, Fst and activin A's implication in metabolic regulation is unclear.Objective: To investigate circulating Fst and activin A in obesity and type 2 diabetes (T2D) and determine their association with metabolic parameters. Further, to examine regulation of Fst and activin A by insulin and the influence of obesity and T2D hereon.Methods: Plasma Fst and activin A levels were analyzed in obese T2D patients (N=10) closely matched to glucose-tolerant lean (N=12) and obese (N=10) individuals in the fasted state and following a 4-hour hyperinsulinemic-euglycemic clamp (40 mU·m-2·min-1) combined with indirect calorimetry.Results: Circulating Fst was ~30% higher in patients with T2D compared with both lean and obese non-diabetic individuals (P <0.001), while plasma activin A was unaltered. In the total cohort, fasting plasma Fst correlated positively with fasting plasma glucose, serum insulin and C-peptide levels, HOMA2-IR, hepatic and adipose tissue insulin resistance after adjusting for age, gender and group (all r >0.47; P <0.05). However, in the individual groups these correlations only achieved significance in patients with T2D (not plasma glucose). Acute hyperinsulinemia at euglycemia reduced circulating Fst by ~30% (P <0.001) and this response was intact in patients with T2D. Insulin inhibited FST expression in human hepatocytes after 2-hours and even further after 48-hours.Conclusions: Elevated circulating Fst, but not activin A, is strongly associated with measures of insulin resistance in patients with T2D. However, the ability of insulin to suppress circulating Fst is preserved in T2D.

AB - Background: Circulating follistatin (Fst) binds activin A and thereby regulates biological functions such as muscle growth and β-cell survival. However, Fst and activin A's implication in metabolic regulation is unclear.Objective: To investigate circulating Fst and activin A in obesity and type 2 diabetes (T2D) and determine their association with metabolic parameters. Further, to examine regulation of Fst and activin A by insulin and the influence of obesity and T2D hereon.Methods: Plasma Fst and activin A levels were analyzed in obese T2D patients (N=10) closely matched to glucose-tolerant lean (N=12) and obese (N=10) individuals in the fasted state and following a 4-hour hyperinsulinemic-euglycemic clamp (40 mU·m-2·min-1) combined with indirect calorimetry.Results: Circulating Fst was ~30% higher in patients with T2D compared with both lean and obese non-diabetic individuals (P <0.001), while plasma activin A was unaltered. In the total cohort, fasting plasma Fst correlated positively with fasting plasma glucose, serum insulin and C-peptide levels, HOMA2-IR, hepatic and adipose tissue insulin resistance after adjusting for age, gender and group (all r >0.47; P <0.05). However, in the individual groups these correlations only achieved significance in patients with T2D (not plasma glucose). Acute hyperinsulinemia at euglycemia reduced circulating Fst by ~30% (P <0.001) and this response was intact in patients with T2D. Insulin inhibited FST expression in human hepatocytes after 2-hours and even further after 48-hours.Conclusions: Elevated circulating Fst, but not activin A, is strongly associated with measures of insulin resistance in patients with T2D. However, the ability of insulin to suppress circulating Fst is preserved in T2D.

KW - Faculty of Science

KW - Follistatin

KW - Activin A

KW - Insulin resistance

KW - Insulin

KW - Type 2 diabetes

U2 - 10.1210/clinem/dgaa090

DO - 10.1210/clinem/dgaa090

M3 - Journal article

C2 - 32112102

VL - 105

SP - 1343

EP - 1354

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 5

ER -

ID: 237513587