ArticleMolecular and cellular biology2004
The NAD(P)H oxidase homolog Nox4 modulates insulin-stimulated generation of H2O2 and plays an integral role in insulin signal transduction.
Article in Molecular and cellular biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 225 papers.
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Who cites it
225 citing papers in PubMed, 505 citations in OpenAlex.
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- Pharmacological Potential of Selenoproteins in the Regulation of Oxidative Stress in Liver Diseases.Pharmaceutics · 2026Review
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- The physiology of MASLD: molecular pathways between liver and adipose tissues.Clinical science (London, England : 1979) · 2025Review
- The Interplay Between Oxidative Stress and Lipid Composition in Obesity-Induced Inflammation: Antioxidants as Therapeutic Agents in Metabolic Diseases.International journal of molecular sciences · 2025Review
- NADPH oxidases: redox regulation of cell homeostasis and disease.Physiological reviews · 2025Review
- Connecting the Dots: Mitochondrial Dysfunction, PCOS, and Insulin Resistance-Insights and Therapeutic Advances.International journal of molecular sciences · 2025Review
- Regulation of Keap1-Nrf2 signaling in health and diseases.Molecular biology reports · 2024Review
- NADPH Oxidase 3: Beyond the Inner Ear.Antioxidants (Basel, Switzerland) · 2024Review
- Chromatographic Analyses of SpirulinaMedicina (Kaunas, Lithuania) · 2023Article
- Fitness correlates of blubber oxidative stress and cellular defences in grey seals (Halichoerus grypus): support for the life-history-oxidative stress theory from an animal model of simultaneous lactation and fasting.Cell stress & chaperones · 2023Article
- Targeting PI3K/Akt signaling in prostate cancer therapy.Journal of cell communication and signaling · 2023Review
- Overexpression of Mitochondrial Catalase within Adipose Tissue Does Not Confer Systemic Metabolic Protection against Diet-Induced Obesity.Antioxidants (Basel, Switzerland) · 2023Article
- Identification and analysis of hub genes of hypoxia-immunity in type 2 diabetes mellitus.Frontiers in genetics · 2023Article
- Acute exercise and high-glucose ingestion elicit dynamic and individualized responses in systemic markers of redox homeostasis.Frontiers in immunology · 2023Article
- Zinc homeostasis and redox alterations in obesity.Frontiers in endocrinology · 2023Review
165 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Insulin stimulation of target cells elicits a burst of H(2)O(2) that enhances tyrosine phosphorylation of the insulin receptor and its cellular substrate proteins as well as distal signaling events in the insulin action cascade. The molecular mechanism coupling the insulin receptor with the cellular oxidant-generating apparatus has not been elucidated. Using reverse transcription-PCR and Northern blot analyses, we found that Nox4, a homolog of gp91phox, the phagocytic NAD(P)H oxidase catalytic subunit, is prominently expressed in insulin-sensitive adipose cells. Adenovirus-mediated expression of Nox4 deletion constructs lacking NAD(P)H or FAD/NAD(P)H cofactor binding domains acted in a dominant-negative fashion in differentiated 3T3-L1 adipocytes and attenuated insulin-stimulated H(2)O(2) generation, insulin receptor (IR) and IRS-1 tyrosine phosphorylation, activation of downstream serine kinases, and glucose uptake. Transfection of specific small interfering RNA oligonucleotides reduced Nox4 protein abundance and also inhibited the insulin signaling cascade. Overexpression of Nox4 also significantly reversed the inhibition of insulin-stimulated IR tyrosine phosphorylation induced by coexpression of PTP1B by inhibiting PTP1B catalytic activity. These data suggest that Nox4 provides a novel link between the IR and the generation of cellular reactive oxygen species that enhance insulin signal transduction, at least in part via the oxidative inhibition of cellular protein-tyrosine phosphatases (PTPases), including PTP1B, a PTPase that has been previously implicated in the regulation of insulin action.
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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 OpenQuestion graph.