ArticlePloS one2014
20-Hydroxyeicosatetraenoic acid impairs endothelial insulin signaling by inducing phosphorylation of the insulin receptor substrate-1 at Ser616.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
What it found
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Who cites it
19 citing papers in PubMed, 33 citations in OpenAlex.
- Gpr75 Deletion in Adipocytes Protects From Diet-Induced Obesity: Changes in Glucose Homeostasis and Inflammatory Responses.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- The machinery of healthy vasoconstriction: an overview.Pflugers Archiv : European journal of physiology · 2025Review
- The role of ERK1/2 signaling in diabetes: pathogenic and therapeutic implications.Frontiers in pharmacology · 2025Review
- Phosphorylation Codes in IRS-1 and IRS-2 Are Associated with the Activation/Inhibition of Insulin Canonical Signaling Pathways.Current issues in molecular biology · 2024Review
- Gpr75-deficient mice are protected from high-fat diet-induced obesity.Obesity (Silver Spring, Md.) · 2023Article
- 20-Hydroxyeicosatetraenoic acid (20-HETE): Bioactions, receptors, vascular function, cardiometabolic disease and beyond.Advances in pharmacology (San Diego, Calif.) · 2023Article
- Oxylipin responses to fasting and insulin infusion in a large mammalian model of fasting-induced insulin resistance, the northern elephant seal.American journal of physiology. Regulatory, integrative and comparative physiology · 2021Article
- Genetics Variants in the Epoxygenase Pathway of Arachidonic Metabolism Are Associated with Eicosanoids Levels and the Risk of Diabetic Nephropathy.Journal of clinical medicine · 2021Article
- 20-HETE interferes with insulin signaling and contributes to obesity-driven insulin resistance.Prostaglandins & other lipid mediators · 2021Article
- Factors associated with platelet reactivity during dual antiplatelet therapy in patients with diabetes after acute coronary syndrome.Scientific reports · 2020Article
- CYP2J2/EET reduces vulnerability to atrial fibrillation in chronic pressure overload mice.Journal of cellular and molecular medicine · 2020Article
- Oxidized HDL, Adipokines, and Endothelial Dysfunction: A Potential Biomarker Profile for Cardiovascular Risk in Women with Obesity.Obesity (Silver Spring, Md.) · 2019Article
- 20-HETE in the regulation of vascular and cardiac function.Pharmacology & therapeutics · 2018Review
- High-fat diet-induced obesity and insulin resistance in CYP4a14American journal of physiology. Regulatory, integrative and comparative physiology · 2018Article
- Coronary microvascular dysfunction in diabetes mellitus.The Journal of international medical research · 2017Review
- Impact of Long-Term Poor and Good Glycemic Control on Metabolomics Alterations in Type 1 Diabetic People.The Journal of clinical endocrinology and metabolism · 2016Article
- Vascular actions of 20-HETE.Prostaglandins & other lipid mediators · 2015Review
- Liraglutide Exerts Antidiabetic Effect via PTP1B and PI3K/Akt2 Signaling Pathway in Skeletal Muscle of KKAy Mice.International journal of endocrinology · 2014Article
Corrections and comments
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Authors and funding
7 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
20-Hydroxyeicosatetraenoic acid (20-HETE) induces endothelial dysfunction and is correlated with diabetes. This study was designed to investigate the effects of 20-HETE on endothelial insulin signaling.Human umbilical vein endothelial cells (HUVECs) or C57BL/6J mice were treated with 20-HETE in the presence or absence of insulin, and p-ERK1/2, p-JNK, IRS-1/PI3K/AKT/eNOS pathway, were examined in endothelial cells and aortas by immunoblotting. eNOS activity and nitric oxide production were measured. 20-HETE increased ERK1/2 phosphorylation and IRS-1 phosphorylation at Ser616; these effects were reversed by ERK1/2 inhibition. We further observed that 20-HETE treatment resulted in impaired insulin-stimulated IRS-1 phosphorylation at Tyr632 and subsequent PI3-kinase/Akt activation. Furthermore, 20-HETE treatment blocked insulin-stimulated phosphorylation of eNOS at the stimulatory Ser1177 site, eNOS activation and NO production; these effects were reversed by inhibiting ERK1/2. Treatment of C57BL/6J mice with 20-HETE resulted in ERK1/2 activation and impaired insulin-dependent activation of the IRS-1/PI3K/Akt/eNOS pathway in the aorta. Our data suggest that the 20-HETE activation of IRS-1 phosphorylation at Ser616 is dependent on ERK1/2 and leads to impaired insulin-stimulated vasodilator effects that are mediated by the IRS-1/PI3K/AKT/eNOS pathway.
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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.