ArticleDiabetes2013
Nox2 NADPH oxidase has a critical role in insulin resistance-related endothelial cell dysfunction.
Article in Diabetes, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 137 citations in OpenAlex.
- Local apocynin improves acetylcholine- but not insulin-mediated vasodilation in the cutaneous microvasculature of women with a history of gestational diabetes.Journal of applied physiology (Bethesda, Md. : 1985) · 2026Article
- A TRPM2-Driven Signalling Cycle Orchestrates Abnormal Inter-Organelle Crosstalk in Cardiovascular and Metabolic Diseases.Biomolecules · 2025Review
- Association of SNPs in carbohydrate metabolism genes with insulin resistance indicators in the Mexican population.Nutrition & metabolism · 2025Article
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Metabolic and vascular insulin resistance: partners in the pathogenesis of cardiovascular disease in diabetes.American journal of physiology. Heart and circulatory physiology · 2025Review
- Role of NOX2 in the regulation of inflammatory and apoptotic pathways in congolese patients with type 2 diabetes in Brazzaville.Frontiers in endocrinology · 2025Article
- Mechanisms of Flavonoids and Their Derivatives in Endothelial Dysfunction Induced by Oxidative Stress in Diabetes.Molecules (Basel, Switzerland) · 2024Review
- Pathological high intraocular pressure induces glial cell reactive proliferation contributing to neuroinflammation of the blood-retinal barrier via the NOX2/ET-1 axis-controlled ERK1/2 pathway.Journal of neuroinflammation · 2024Article
- Whole-body insulin resistance leads to accelerated atherosclerosis: role for Nox2 NADPH oxidase.Vascular biology (Bristol, England) · 2024Article
- CircRNA7632 down-regulation alleviates endothelial cell dysfunction in Kawasaki disease via regulating IL-33 expression.Cell stress & chaperones · 2023Article
- Specific inhibition of NADPH oxidase 2 modifies chronic epilepsy.Redox biology · 2022Article
- Effects of Polyphenols on Glucose-Induced Metabolic Changes in Healthy Human Subjects and on Glucose Transporters.Molecular nutrition & food research · 2022Review
- Inhibiting NADPH Oxidases to Target Vascular and Other Pathologies: An Update on Recent Experimental and Clinical Studies.Biomolecules · 2022Review
- Recent developments in the structural characterisation of the IR and IGF1R: implications for the design of IR-IGF1R hybrid receptor modulators.RSC medicinal chemistry · 2022Review
- Ceramides and other sphingolipids as drivers of cardiovascular disease.Nature reviews. Cardiology · 2021Review
- Novel Paracrine Action of Endothelium Enhances Glucose Uptake in Muscle and Fat.Circulation research · 2021Article
- Review
- From diabetes to renal aging: the therapeutic potential of adiponectin.Journal of physiology and biochemistry · 2021Review
- Endothelial Nox5 Expression Modulates Glucose Uptake and Lipid Accumulation in Mice Fed a High-Fat Diet and 3T3-L1 Adipocytes Treated with Glucose and Palmitic Acid.International journal of molecular sciences · 2021Article
- Coordinated Contribution of NADPH Oxidase- and Mitochondria-Derived Reactive Oxygen Species in Metabolic Syndrome and Its Implication in Renal Dysfunction.Frontiers in pharmacology · 2021Review
13 more citing papers are in PubMed but not listed here.
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Authors and funding
17 authors at 1 institution in 1 country.
Funding
Abstract
Insulin resistance is characterized by excessive endothelial cell generation of potentially cytotoxic concentrations of reactive oxygen species. We examined the role of NADPH oxidase (Nox) and specifically Nox2 isoform in superoxide generation in two complementary in vivo models of human insulin resistance (endothelial specific and whole body). Using three complementary methods to measure superoxide, we demonstrated higher levels of superoxide in insulin-resistant endothelial cells, which could be pharmacologically inhibited both acutely and chronically, using the Nox inhibitor gp91ds-tat. Similarly, insulin resistance-induced impairment of endothelial-mediated vasorelaxation could also be reversed using gp91ds-tat. siRNA-mediated knockdown of Nox2, which was specifically elevated in insulin-resistant endothelial cells, significantly reduced superoxide levels. Double transgenic mice with endothelial-specific insulin resistance and deletion of Nox2 showed reduced superoxide production and improved vascular function. This study identifies Nox2 as the central molecule in insulin resistance-mediated oxidative stress and vascular dysfunction. It also establishes pharmacological inhibition of Nox2 as a novel therapeutic target in insulin resistance-related vascular disease.
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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.