Circulating follistatin and activin A and their regulation by insulin in obesity and type 2 diabetes
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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.
In: Journal of Clinical Endocrinology and Metabolism, Vol. 105, No. 5, 2020, p. 1343-1354.Research output: Contribution to journal › Journal article › Research › peer-review
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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