ArticleNature communications2021
Paracrine FGFs target skeletal muscle to exert potent anti-hyperglycemic effects.
Article in Nature communications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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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.
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Who cites it
37 citing papers in PubMed, 68 citations in OpenAlex.
- Microvascular insulin resistance with enhanced muscle glucose disposal in CD36 deficiency.Diabetologia · 2025Trial
- Review
- State-Dependent FGF Signaling in Satellite Cell-Mediated Skeletal Muscle Regeneration and Pathological Remodeling.Biomolecules · 2026Review
- Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks.International journal of molecular sciences · 2026Review
- Acute Hyperinsulinemia during Hyperinsulinemic- Euglycemic Clamp Influences DNA Methylation and Gene Expression in Peripheral Blood Cells of Adult Men.Diabetes & metabolism journal · 2026Article
- FGF21 targets pathways which enhance insulin sensitivity in brown adipose but not skeletal muscle in mice.Endocrinology · 2026Article
- FGF4 activates FGFR1 - PI3K/AKT signaling to enhance Clec10a-mediated intracellular myelin debris processing and promote spinal cord repair.Journal of neuroinflammation · 2026Article
- FGF1 ameliorates hepatic steatosis through acute activation of the unfolded protein response and VLDL production.JHEP reports : innovation in hepatology · 2026Article
- The role of fibroblast growth factors in cell and cancer metabolism.FEBS letters · 2026Review
- Breast Cancer Progression by the FGF/FGFR Axis: A Metabolic Perspective.Journal of mammary gland biology and neoplasia · 2025Review
- FGF4-FGFR1 signaling promotes podocyte survival and glomerular function to ameliorate diabetic kidney disease in male mice.Nature communications · 2025Article
- Downregulation of ubiquitous microRNA-320 in hepatocytes triggers RFX1-mediated FGF1 suppression to accelerate MASH progression.Acta pharmaceutica Sinica. B · 2025Article
- Development of FGF21 Mutant with Potent Cardioprotective Effects in T2D Mice via FGFR1-AMPK-Mediated Inhibition of Oxidative Stress.International journal of molecular sciences · 2025Article
- FGF-based drug discovery: advances and challenges.Nature reviews. Drug discovery · 2025Review
- Role of acitretin in regulating glucose and lipid homeostasis in an imiquimod-induced psoriasis model mouse.Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Article
- Complex interplay between type 2 diabetes mellitus and pancreatic cancer: insights from observational and mendelian randomization analyses.BMC cancer · 2025Observational
- Flavonoid-Rich Extracts from Chuju (Foods (Basel, Switzerland) · 2025Article
- Blood-Based Whole-Genome Methylation Analysis of Yili Horses Pre- and Post-Racing.Animals : an open access journal from MDPI · 2025Article
- The impact of physical activity and dietary habits on glycolipemic metabolism and inflammatory markers in the elderly: a cross-sectional study.Frontiers in nutrition · 2025Article
- Eye on the horizon: The metabolic landscape of the RPE in aging and disease.Progress in retinal and eye research · 2025Review
Corrections and comments
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Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Several members of the FGF family have been identified as potential regulators of glucose homeostasis. We previously reported that a low threshold of FGF-induced FGF receptor 1c (FGFR1c) dimerization and activity is sufficient to evoke a glucose lowering activity. We therefore reasoned that ligand identity may not matter, and that besides paracrine FGF1 and endocrine FGF21, other cognate paracrine FGFs of FGFR1c might possess such activity. Indeed, via a side-by-side testing of multiple cognate FGFs of FGFR1c in diabetic mice we identified the paracrine FGF4 as a potent anti-hyperglycemic FGF. Importantly, we found that like FGF1, the paracrine FGF4 is also more efficacious than endocrine FGF21 in lowering blood glucose. We show that paracrine FGF4 and FGF1 exert their superior glycemic control by targeting skeletal muscle, which expresses copious FGFR1c but lacks β-klotho (KLB), an obligatory FGF21 co-receptor. Mechanistically, both FGF4 and FGF1 upregulate GLUT4 cell surface abundance in skeletal muscle in an AMPKα-dependent but insulin-independent manner. Chronic treatment with rFGF4 improves insulin resistance and suppresses adipose macrophage infiltration and inflammation. Notably, unlike FGF1 (a pan-FGFR ligand), FGF4, which has more restricted FGFR1c binding specificity, has no apparent effect on food intake. The potent anti-hyperglycemic and anti-inflammatory properties of FGF4 testify to its promising potential for use in the treatment of T2D and related metabolic disorders.
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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.