ArticleThe Journal of biological chemistry
Inhibition of soluble epoxide hydrolase alleviates insulin resistance and hypertension via downregulation of SGLT2 in the mouse kidney.
Article in The Journal of biological chemistry. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- The blood pressure-lowering effect of an anti-soluble epoxide hydrolase vaccine in angiotensin II-induced hypertension in mice.Hypertension research : official journal of the Japanese Society of Hypertension · 2026Article
- Bioactive constituents isolated from the leaves of Phyllostachys Bambusoides with potent soluble epoxide hydrolase inhibitory activity: enzyme kinetics, molecular docking, and molecular dynamics simulations.Journal of computer-aided molecular design · 2025Article
- Epoxide Hydrolase Inhibitors for the Treatment of Alzheimer's Disease and Other Neurological Disorders: A Comprehensive Review.Biomedicines · 2025Review
- Article
- Inhibition of soluble epoxide hydrolase in endotoxin induced pig lung injury.Frontiers in pharmacology · 2025Article
- Inhibition of Soluble Epoxide Hydrolase Ameliorates Cerebral Blood Flow Autoregulation and Cognition in Alzheimer's Disease and Diabetes-Related Dementia Rat Models.bioRxiv : the preprint server for biology · 2024Article
- SGLT2 inhibition, plasma proteins, and heart failure: a proteome-wide Mendelian Randomization and colocalization study.Frontiers in cardiovascular medicine · 2024Article
- Study on the correlation between the level of insulin resistance and changes in the degree of cerebral atherosclerosis in non-diabetic patients.Technology and health care : official journal of the European Society for Engineering and Medicine · 2024Article
- Role of soluble epoxide hydrolase in the abnormal activation of fibroblast-like synoviocytes from patients with rheumatoid arthritis.Clinical immunology (Orlando, Fla.) · 2023Article
- Integration of plasma and CSF metabolomics with CSF proteomic reveals novel associations between lipid mediators and central nervous system vascular and energy metabolism.Scientific reports · 2023Article
- Article
- Hypertension in Patients with Insulin Resistance: Etiopathogenesis and Management in Children.International journal of molecular sciences · 2022Review
- SMTP-44D Exerts Antioxidant and Anti-Inflammatory Effects through Its Soluble Epoxide Hydrolase Inhibitory Action in Immortalized Mouse Schwann Cells upon High Glucose Treatment.International journal of molecular sciences · 2022Article
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epoxyeicosatrienoic acid (EET) exerts beneficial effects on insulin resistance and/or hypertension. EETs could be readily converted to less biological active diols by soluble epoxide hydrolase (sEH). However, whether sEH inhibition can ameliorate the comorbidities of insulin resistance and hypertension and the underlying mechanisms of this relationship are unclear. In this study, C57BL/6 mice were rendered hypertensive and insulin resistant through a high-fat and high-salt (HF-HS) diet. The sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), was used to treat mice (1 mg/kg/day) for 8 weeks, followed by analysis of metabolic parameters. The expression of sEH and the sodium-glucose cotransporter 2 (SGLT2) was markedly upregulated in the kidneys of mice fed an HF-HS diet. We found that TPPU administration increased kidney EET levels, improved insulin resistance, and reduced hypertension. Furthermore, TPPU treatment prevented upregulation of SGLT2 and the associated increased urine volume and the excretion of urine glucose and urine sodium. Importantly, TPPU alleviated renal inflammation. In vitro, human renal proximal tubule epithelial cells (HK-2 cells) were used to further investigate the underlying mechanism. We observed that 14,15-EET or sEH knockdown or inhibition prevented the upregulation of SGLT2 upon treatment with palmitic acid or NaCl by inhibiting the inhibitory kappa B kinase α/β/NF-κB signaling pathway. In conclusion, sEH inhibition by TPPU alleviated insulin resistance and hypertension induced by an HF-HS diet in mice. The increased urine excretion of glucose and sodium was mediated by decreased renal SGLT2 expression because of inactivation of the inhibitory kappa B kinase α/β/NF-κB-induced inflammatory response.
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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.