ArticleEBioMedicine2019
Liver-derived fibroblast growth factor 21 mediates effects of glucagon-like peptide-1 in attenuating hepatic glucose output.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 79 citations in OpenAlex.
- Reduction of Hepatic Fat Content by Dulaglutide for the Treatment of Diabetes Mellitus: A Two-Centre Open, Single-Arm Trial.Endocrinology, diabetes & metabolism · 2025Trial
- Effects of exenatide on urinary albumin in overweight/obese patients with T2DM: a randomized clinical trial.Scientific reports · 2021Trial
- Glucagon-like peptide-1: a critical link between gut microbiota dysbiosis and degenerative musculoskeletal diseases.Gut microbes · 2026Review
- Key Hepatokines Linking MASLD and Type 2 Diabetes: From Pathophysiological Mechanisms to Therapeutic Modulation.International journal of molecular sciences · 2026Review
- GLP-1 receptor agonists in metabolic dysfunction-associated steatotic liver disease: mechanistic networks and translational implications: a review.Journal of endocrinological investigation · 2026Review
- HFpEF and MASLD: converging mechanisms and clinical implications.Nature reviews. Cardiology · 2026Review
- Hypothalamus-liver talks: whispers in the language of metabolism.Reviews in endocrine & metabolic disorders · 2026Review
- Circulating GDF15 and HbA1c Response to Add-On Exenatide Therapy in Type 2 Diabetes: A Post Hoc Analysis from a Multicenter Trial.Biomedicines · 2026Article
- FGF21 analogue PF-05231023 on alcohol consumption and neuronal activity in the nucleus accumbens.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2026Article
- Changes in fibroblast growth factor 21 levels associated with alcohol consumption and smoking cessation.Endocrine connections · 2026Article
- GLP-1 receptor agonists show no detrimental effect on sperm quality in mouse models and cell lines.Endocrine · 2025Article
- Hepatic fibroblast growth factor 21 is required for curcumin or resveratrol in exerting their metabolic beneficial effect in male mice.Nutrition & diabetes · 2025Article
- Use of GLP-1 Receptor Agonists for the Management of Type 1 Diabetes: A Pediatric Perspective.Hormone research in paediatrics · 2025Review
- Hepatokines and MASLD: The GLP1-Ras-FGF21-Fetuin-A Crosstalk as a Therapeutic Target.International journal of molecular sciences · 2024Review
- Hepatic function of glucagon-like peptide-1 and its based diabetes drugs.Medical review (2021) · 2024Review
- Weight-loss maintenance is accompanied by interconnected alterations in circulating FGF21-adiponectin-leptin and bioactive sphingolipids.Cell reports. Medicine · 2024Article
- Defective FGFR1 Signaling Disrupts Glucose Regulation: Evidence From Humans WithJournal of the Endocrine Society · 2024Article
- Gut Microbiota-Tryptophan Metabolism-GLP-1 Axis Participates in β-Cell Regeneration Induced by Dapagliflozin.Diabetes · 2024Article
- Fibroblast growth factor 21: An emerging pleiotropic regulator of lipid metabolism and the metabolic network.Genes & diseases · 2024Review
- Advances in management of metabolic dysfunction-associated steatotic liver disease: from mechanisms to therapeutics.Lipids in health and disease · 2024Review
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundGlucagon-like peptide-1 (GLP-1) and its based agents improve glycemic control. Although their attenuating effect on hepatic glucose output has drawn our attention for decades, the potential mechanisms remain unclear.
methodsCytokine array kit was used to assess cytokine profiles in db/db mice and mouse primary hepatocytes treated with exenatide (exendin-4). Two diabetic mouse models (db/db and Pax6
findingsUtilizing the cytokine array, we identified that FGF21 secretion was upregulated by exenatide (exendin-4). Similarly, FGF21 production in hepatocytes was stimulated by exenatide or liraglutide. FGF21 blockage attenuated the inhibitory effects of the GLP-1 analogs on hepatic glucose output. Similar results were also observed in primary hepatocytes from Fgf21 knockout mice. Furthermore, exenatide treatment increased serum FGF21 level in patients with T2D, particularly in those with better glucose control.
interpretationWe identify that function of GLP-1 in inhibiting hepatic glucose output is mediated via the liver hormone FGF21. Thus, we provide a new extra-pancreatic mechanism by which GLP-1 regulates glucose homeostasis. FUND: National Key Research and Development Program of China, the National Natural Science Foundation of China, the Natural Science Foundation of Beijing and Peking University Medicine Seed Fund for Interdisciplinary Research.
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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 Socratic graph.