ArticleMolecular metabolism2015
Glucagon-to-insulin ratio is pivotal for splanchnic regulation of FGF-21 in humans.
Article in Molecular metabolism, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 1 of them a synthesis that pooled it.
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Who cites it
69 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Exercise-Induced Fibroblast Growth Factor-21: A Systematic Review and Meta-Analysis.International journal of molecular sciences · 2023Pooled it
- Effect of exercise on Fibroblast Growth Factor 21 levels in healthy males and females.PloS one · 2025Trial
- Trial
- Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated With Protein Ingestion-Induced Insulin Resistance.Diabetes · 2017Trial
- Effect of Pancreatic Hormones on pro-Atrial Natriuretic Peptide in Humans.EBioMedicine · 2017Trial
- Lipid nanoparticle-mediated transcription factor EB mRNA delivery for the treatment of metabolic dysfunction-associated steatotic liver disease.Molecular biomedicine · 2026Article
- Review
- Exerkine-Mediated Inter-Organ Crosstalk and Translational Perspectives in Metabolic Diseases.Current obesity reports · 2026Review
- Multidisciplinary Therapy to Target Obesity and Its Complications in Adult Population: A Narrative Review.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2026Review
- Fibroblast Growth Factor 21: Bridging Nutrient Stress Signaling and Exercise-Induced Adaptive Responses.Diabetes & metabolism journal · 2026Article
- Exercise Training Stimulates the Release of Glutathione Peroxidase 1 (GPX1)-Enriched Extracellular Vesicles That Promote Angiogenesis.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Mechanistic insights into the liver-brain axis during chronic liver disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Physical activity and improvement of physiological parameters by training.Frontiers in sports and active living · 2026Review
- Secreted proteins in treating metabolic dysfunction-associated steatotic liver disease: from bench towards bedside.Protein & cell · 2025Review
- Housing temperature influences exercise-induced glucose regulation and expression of exerkines in mice.Experimental physiology · 2025Article
- Relationship between glucagon and metabolic dysfunction-associated steatotic liver disease in patients with type 2 diabetes mellitus.World journal of hepatology · 2025Article
- Research progress on the role of FGF21 in insulin resistance.Frontiers in endocrinology · 2025Review
- Targeting fibroblast growth factor (FGF)-21: a promising strategy for metabolic dysfunction-associated steatotic liver disease treatment.Frontiers in pharmacology · 2025Review
- Effect of a 6-Week Carbohydrate-Reduced High-Protein Diet on Levels of FGF21 and GDF15 in People With Type 2 Diabetes.Journal of the Endocrine Society · 2024Article
- Inter-organ crosstalk during development and progression of type 2 diabetes mellitus.Nature reviews. Endocrinology · 2024Review
9 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsFibroblast growth factor 21 (FGF-21) is a liver-derived metabolic regulator induced by energy deprivation. However, its regulation in humans is incompletely understood. We addressed the origin and regulation of FGF-21 secretion in humans.
methodsBy determination of arterial-to-venous differences over the liver and the leg during exercise, we evaluated the organ-specific secretion of FGF-21 in humans. By four different infusion models manipulating circulating glucagon and insulin, we addressed the interaction of these hormones on FGF-21 secretion in humans.
resultsWe demonstrate that the splanchnic circulation secretes FGF-21 at rest and that it is rapidly enhanced during exercise. In contrast, the leg does not contribute to the systemic levels of FGF-21. To unravel the mechanisms underlying the regulation of exercise-induced hepatic release of FGF-21, we manipulated circulating glucagon and insulin. These studies demonstrated that in humans glucagon stimulates splanchnic FGF-21 secretion whereas insulin has an inhibitory effect.
conclusionsCollectively, our data reveal that 1) in humans, the splanchnic bed contributes to the systemic FGF-21 levels during rest and exercise; 2) under normo-physiological conditions FGF-21 is not released from the leg; 3) a dynamic interaction of glucagon-to-insulin ratio regulates FGF-21 secretion in humans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.