ArticleDiabetes2021
EET Analog Treatment Improves Insulin Signaling in a Genetic Mouse Model of Insulin Resistance.
Article in Diabetes, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Alterations in Epoxyeicosatrienoic Acids Metabolism in Type 2 Diabetes Mellitus and Potential Association with Retinopathy Progression.Current medicinal chemistry · 2026Article
- Bioinformatics analyses of comorbid mechanisms between psoriasis and type 2 diabetes mellitus.Scientific reports · 2025Article
- Structure-Based Design and Optimization Lead to the Identification of a Novel Potent sEH Inhibitor with PPARγ Partial Agonist Activity against Inflammatory and Metabolic-Related Diseases.Journal of medicinal chemistry · 2025Article
- Epoxyeicosatrienoic acids (EETs): A novel class of second messengers of hormonal functional responses.Prostaglandins & other lipid mediators · 2025Review
- Article
- The interplay of inflammation and placenta in maternal diabetes: insights into Hofbauer cell expression patterns.Frontiers in immunology · 2024Article
- A Review: Cytochrome P450 in Alcoholic and Non-Alcoholic Fatty Liver Disease.Diabetes, metabolic syndrome and obesity : targets and therapy · 2024Review
- Effects of UBE3A on the insulin resistance in polycystic ovary syndrome through the ubiquitination of AMPK.BMC endocrine disorders · 2023Article
- Recent Advances in the Treatment of Insulin Resistance Targeting Molecular and Metabolic Pathways: Fighting a Losing Battle?Medicina (Kaunas, Lithuania) · 2022Review
- Molecular mechanism of benzo [a] pyrene regulating lipid metabolism via aryl hydrocarbon receptor.Lipids in health and disease · 2022Article
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
We previously showed that global deletion of the cytochrome P450 epoxygenase Cyp2c44, a major epoxyeicosatrienoic acid (EET) producing enzyme in mice, leads to impaired hepatic insulin signaling resulting in insulin resistance. This finding led us to investigate whether administration of a water soluble EET analog restores insulin signaling in vivo in Cyp2c44(-/-) mice and investigated the underlying mechanisms by which this effect is exerted. Cyp2c44(-/-) mice treated with the analog EET-A for 4 weeks improved fasting glucose and glucose tolerance compared to Cyp2c44(-/-) mice treated with vehicle alone. This beneficial effect was accompanied by enhanced hepatic insulin signaling, decreased expression of gluconeogenic genes and increased expression of glycogenic genes. Mechanistically, we show that insulin-stimulated phosphorylation of insulin receptor β (IRβ) is impaired in primary Cyp2c44(-/-) hepatocytes and this can be restored by cotreatment with EET-A and insulin. Plasma membrane fractionations of livers indicated that EET-A enhances the retention of IRβ in membrane rich fractions, thus potentiating its activation. Altogether, EET analogs ameliorate insulin signaling in a genetic model of hepatic insulin resistance by stabilizing membrane-associated IRβ and potentiating insulin signaling.
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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.