ArticleDiabetologia2013
Glucagon increases circulating fibroblast growth factor 21 independently of endogenous insulin levels: a novel mechanism of glucagon-stimulated lipolysis?
Article in Diabetologia, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03139305 (Effect of Prolonged), which is not on this map. Cited by 35 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Effect of Prolonged (72 Hour) Glucagon Administration on Energy Expenditure in Healthy Obese Subjects
Who cites it
35 citing papers in PubMed, 90 citations in OpenAlex.
- Meal sugar-protein balance determines postprandial FGF21 response in humans.American journal of physiology. Endocrinology and metabolism · 2023Trial
- Alterations in 3-Hydroxyisobutyrate and FGF21 Metabolism Are Associated With Protein Ingestion-Induced Insulin Resistance.Diabetes · 2017Trial
- Glucagon regulates orexin A secretion in humans and rodents.Diabetologia · 2014Trial
- Adipose Tissue, at the Core of the Action of Incretin and Glucagon-Based Anti-Obesity Drugs.Current obesity reports · 2025Review
- Research progress on the role of FGF21 in insulin resistance.Frontiers in endocrinology · 2025Review
- The dual GLP-1/glucagon receptor agonist G49 mimics bariatric surgery effects by inducing metabolic rewiring and inter-organ crosstalk.Nature communications · 2024Article
- Glucagon resistance and metabolic-associated steatotic liver disease: a review of the evidence.The Journal of endocrinology · 2024Review
- The potential effect of metformin on fibroblast growth factor 21 in type 2 diabetes mellitus (T2DM).Inflammopharmacology · 2023Review
- Glucagon receptor signaling at white adipose tissue does not regulate lipolysis.American journal of physiology. Endocrinology and metabolism · 2022Article
- The stimulatory effects of glucagon on cortisol and GH secretion occur independently from FGF-21.Endocrine · 2022Article
- Is Glucagon Receptor Activation the Thermogenic Solution for Treating Obesity?Frontiers in endocrinology · 2022Review
- The Regulation of Circulating Hepatokines by Fructose Ingestion in Humans.Journal of the Endocrine Society · 2021Article
- Glucagon Reduces Neutrophil Migration and Increases Susceptibility to Sepsis in Diabetic Mice.Frontiers in immunology · 2021Article
- Glucagon-Dependent Suppression of mTORC1 is Associated with Upregulation of Hepatic FGF21 mRNA Translation.American journal of physiology. Endocrinology and metabolism · 2020Article
- Leveraging the Gut to Treat Metabolic Disease.Cell metabolism · 2020Review
- Butyrate attenuated fat gain through gut microbiota modulation in db/db mice following dapagliflozin treatment.Scientific reports · 2019Article
- The brown adipose tissue glucagon receptor is functional but not essential for control of energy homeostasis in mice.Molecular metabolism · 2019Article
- Hepatokines-a novel group of exercise factors.Pflugers Archiv : European journal of physiology · 2019Review
- Current perspective on the role of insulin and glucagon in the pathogenesis and treatment of type 2 diabetes mellitus.Clinical pharmacology : advances and applications · 2019Review
- Running on mixed fuel-dual agonistic approach of GLP-1 and GCG receptors leads to beneficial impact on body weight and blood glucose control: A comparative study between mice and non-human primates.Diabetes, obesity & metabolism · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
aims/hypothesisGlucagon reduces body weight by modifying food intake, glucose/lipid metabolism and energy expenditure. All these physiological processes are also controlled by fibroblast growth factor 21 (FGF-21), a circulating hepatokine that improves the metabolic profile in obesity and type 2 diabetes. Animal experiments have suggested a possible interaction between glucagon and FGF-21 however, the metabolic consequences of this crosstalk are not understood.
methodsThe effects of exogenous glucagon on plasma FGF-21 levels and lipolysis were evaluated in healthy volunteers and humans with type 1 diabetes, as well as in rodents with streptozotocin (STZ)-induced insulinopenic diabetes. In vitro, the role of glucagon on FGF-21 secretion and lipolysis was studied using isolated primary rat hepatocytes and adipocytes. Fgf-21 expression in differentiated rat pre-adipocytes was suppressed by small interfering RNA and released FGF-21 was immunoneutralised by polyclonal antibodies.
resultsGlucagon induced lipolysis in healthy human volunteers, patients with type 1 diabetes, mice and rats with STZ-induced insulinopenic diabetes, and in adipocytes isolated from diabetic and non-diabetic animals. In addition, glucagon increased circulating FGF-21 in healthy humans and rodents, as well as in patients with type 1 diabetes, and insulinopenic rodents. Glucagon stimulated FGF-21 secretion from isolated primary hepatocytes and adipocytes derived from animals with insulinopenic diabetes. Furthermore, FGF-21 stimulated lipolysis in primary adipocytes isolated from non-diabetic and diabetic rats. Reduction of Fgf-21 expression (by approximately 66%) or immunoneutralisation of released FGF-21 markedly attenuated glucagon-stimulated lipolysis in adipocytes. CONCLUSIONS/
interpretationThese results indicate that glucagon increases circulating FGF-21 independently of endogenous insulin levels. FGF-21 participates in glucagon-induced stimulation of lipolysis.
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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.