ArticleCell death & disease2019
Fibroblast growth factor 21 Ameliorates diabetes-induced endothelial dysfunction in mouse aorta via activation of the CaMKK2/AMPKα signaling pathway.
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Pooled it
- Mechanisms and therapeutic potential of AMPK signaling pathway in the regulation of lipid metabolism.Molecular biology reports · 2026Review
- Caffeine Sodium Benzoate-Induced Macrophage M1 Polarization Promotes Endothelial Progenitor Cell Dysfunction by Inducing Mitochondrial Dysfunction Via Targeting let-7a-5p/OPA1 Axis.Applied biochemistry and biotechnology · 2026Article
- Plasma FGF21 is associated with intracranial atherosclerotic stenosis in patients with type 2 diabetes mellitus.Frontiers in neurology · 2026Article
- 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
- Mechanisms of endothelial senescence and vascular aging.Biogerontology · 2025Review
- Targeting neurotrophic dysregulation in diabetic retinopathy: a novel therapeutic avenue.Molecular biology reports · 2025Review
- High Glucose Treatment Induces Nuclei Aggregation of Microvascular Endothelial Cells via theArteriosclerosis, thrombosis, and vascular biology · 2025Article
- Improvements in Exercise for Alzheimer's Disease: Highlighting FGF21-Induced Cerebrovascular Protection.Neurochemical research · 2025Review
- Baihu Jia Renshen Decoction may improve skeletal muscle and adipose tissue functions of type I diabetic rats by affecting pancreatic β-cell function.Genes & genomics · 2025Article
- EndothelialCurrent diabetes reviews · 2025Review
- New concepts in the roles of AMPK in adipocyte stem cell biology.Essays in biochemistry · 2024Review
- The role of nonmyocardial cells in the development of diabetic cardiomyopathy and the protective effects of FGF21: a current understanding.Cell communication and signaling : CCS · 2024Review
- The role of FGF-21 in promoting diabetic wound healing by modulating high glucose-induced inflammation.Heliyon · 2024Article
- Roles of fibroblast growth factors in the treatment of diabetes.World journal of diabetes · 2024Review
- Diabetes Mellitus to Accelerated Atherosclerosis: Shared Cellular and Molecular Mechanisms in Glucose and Lipid Metabolism.Journal of cardiovascular translational research · 2024Review
- Multifaced roles of adipokines in endothelial cell function.Frontiers in endocrinology · 2024Review
- Downregulated calmodulin expression contributes to endothelial cell impairment in diabetes.Acta pharmacologica Sinica · 2023Article
- CaMKK2 as an emerging treatment target for bipolar disorder.Molecular psychiatry · 2023Review
- New Dawn for Atherosclerosis: Vascular Endothelial Cell Senescence and Death.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
17 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Endothelial dysfunction initiates and exacerbates hypertension, atherosclerosis and other cardiovascular complications in diabetic mellitus. FGF21 is a hormone that mediates a number of beneficial effects relevant to metabolic disorders and their associated complications. Nevertheless, it remains unclear as to whether FGF21 ameliorates endothelial dysfunction. Therefore, we investigated the effect of FGF21 on endothelial function in both type 1 and type 2 diabetes. We found that FGF21 reduced hyperglycemia and ameliorated insulin resistance in type 2 diabetic mice, an effect that was totally lost in type 1 diabetic mice. However, FGF21 activated AMPKα, suppressing oxidative stress and enhancing endothelium-dependent vasorelaxation of aorta in both types, suggesting a mechanism that is independent of its glucose-lowering and insulin-sensitizing effects. In vitro, we identified a direct action of FGF21 on endothelial cells of the aorta, in which it bounds to FGF receptors to alleviate impaired endothelial function challenged with high glucose. Furthermore, the CaMKK2-AMPKα signaling pathway was activated to suppress oxidative stress. Apart from its anti-oxidative capacity, FGF21 activated eNOS to dilate the aorta via CaMKK2/AMPKα activation. Our data suggest expanded potential uses of FGF21 for the treatment of vascular diseases in diabetes.
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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.