Cited by 106Fibroblast Growth Factor ResearchAdipokines, Inflammation, and Metabolic DiseasesPhysical Activity and Health

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Exercise-Induced Secretion of FGF21 and Follistatin Are Blocked by Pancreatic Clamp and Impaired in Type 2 Diabetes

Hansen, Jakob Schiøler, Pedersen, Bente Klarlund, Xu, Guowang, Lehmann, Rainer, Weigert, Cora, Plomgaard, Peter·2016·The Journal of Clinical Endocrinology & Metabolism

DOI 10.1210/jc.2016-1681

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Abstract

CONTEXT: Hepatokines have emerged as liver-derived hormone-like factors. Plasma fibroblast growth factor (FGF)-21 and follistatin increase with a high glucagon to insulin ratio and exercise, and resting levels are elevated in patients with type 2 diabetes (T2D). OBJECTIVE: The objective of the study was to investigate the regulatory roles of glucagon to insulin ratio and T2D on exercise-induced FGF21 and follistatin secretion. Design /Interventions: Young healthy males performed a 2-hour bicycle exercise bout followed by 5 hours of rest in supine position with and without a pancreatic clamp blocking the increase in the glucagon to insulin ratio. In addition, we evaluated exercise-induced plasma FGF21 and follistatin in patients with T2D compared with healthy controls in response to 1 hour of bicycle exercise followed by a 3-hour recovery period. RESULTS: In healthy individuals, we observed a 10-fold (P < .002) increase in the glucagon to insulin ratio during exercise, which was abolished by the pancreatic clamp. Exercise with the pancreatic clamp completely blunted the exercise-induced increase in FGF21 (P = .007), whereas the induction of follistatin was approximately 50% reduced (P = .04). Exercise-induced FGF21 secretion was completely absent in patients with T2D, whereas the exercise-induced follistatin increase was impaired. CONCLUSIONS/INTERPRETATION: Exercise-induced increases in plasma FGF21 and follistatin are attenuated by the pancreatic clamp, indicating important roles for glucagon and insulin as upstream regulators. For follistatin, an additional regulatory mechanism must exist. Our data further show that exercise-induced FGF21 and follistatin secretion are impaired in patients with T2D. The magnitude of changes in glucagon and insulin or the sensitivity to these hormones seems central in the regulation of FGF21 and follistatin in humans.

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Authors: Hansen, J. S., Pedersen, B. K., Xu, G., Lehmann, R., Weigert, C., & Plomgaard, P.
Affiliations: University of Copenhagen (DK)
Corresponding author: Plomgaard, Peter
ORCID: Pedersen, Bente Klarlund
Xu, Guowang
Lehmann, Rainer
Weigert, Cora
Plomgaard, Peter
Venue: The Journal of Clinical Endocrinology & Metabolism
Publisher: The Endocrine Society
Published: 2016-07
Volume: 101
Issue: 7
Pages: 2816-2825
ISSN: 0021-972X (ISSN-L)
1945-7197
DOI: 10.1210/jc.2016-1681
OpenAlex: W2375156733
Cited by: 106
References: 35
Citations by year: 2026: 6 · 2025: 7 · 2024: 6 · 2023: 13 · 2022: 9 · 2021: 17 · 2020: 15 · 2019: 9 · 2018: 12 · 2017: 8 · 2016: 4
FWCI: 5.72
Type: journal article
Language: en
Open access: closed
Locations: The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
PubMed (publishedVersion)
Dalian Institute of Chemical Physics, CAS Institutional Repository (submittedVersion)
Site cant be reached (submittedVersion)
Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
PuSH - Publication Server of Helmholtz Zentrum München (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Physical Activity and Health
Keywords: FGF21, follistatin, hepatic hormones, physical activity, type 2 diabetes, glucagon, insulin, hormonal regulation
MeSH terms: Adult, Diabetes Mellitus, Type 2, Fibroblast Growth Factors, Glucagon, Humans, Insulin, Insulin Resistance, Male, Pancreas, Glucose Clamp Technique, Exercise, Cross-Over Studies, Follistatin, Young Adult

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Exercise-Induced Secretion of FGF21 and Follistatin Are Blocked by Pancreatic Clamp and Impaired in Type 2 Diabetes

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