ArticlePloS one2010
Endotoxin mediated-iNOS induction causes insulin resistance via ONOO⁻ induced tyrosine nitration of IRS-1 in skeletal muscle.
Article in PloS one, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 71 citations in OpenAlex.
- Endothelial nitric oxide signaling in cellular and systemic metabolism.Redox biology · 2026Review
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- Metabolic dysfunction-associated steatotic liver disease: A story of muscle and mass.World journal of gastroenterology · 2025Article
- Cysteine residues in signal transduction and its relevance in pancreatic beta cells.Frontiers in endocrinology · 2023Review
- Interplay of carbon dioxide and peroxide metabolism in mammalian cells.The Journal of biological chemistry · 2022Review
- Enrichment of Newly Synthesized Proteins following treatment of C2C12 Myotubes with Endotoxin and Interferon-γ.Inflammation · 2022Article
- In vitro toxic interaction of arsenic and hyperglycemia in mitochondria: an important implication of increased vulnerability in pre-diabetics.Environmental science and pollution research international · 2022Article
- Mechanisms affecting brain remodeling in depression: do all roads lead to impaired fibrinolysis?Molecular psychiatry · 2022Review
- Inducible nitric oxide synthase: Regulation, structure, and inhibition.Medicinal research reviews · 2020Review
- Tracking changes of the parameters of glucose-insulin homeostasis during the course of obesity in B6D2F1 mice.Heliyon · 2020Article
- Cytokines promote lipolysis in 3T3-L1 adipocytes through induction of NADPH oxidase 3 expression and superoxide production.Journal of lipid research · 2018Article
- Environmental Toxicant Exposures and Type 2 Diabetes Mellitus: Two Interrelated Public Health Problems on the Rise.Current opinion in toxicology · 2018Article
- High-fat diet-induced obesity impairs insulin signaling in lungs of allergen-challenged mice: Improvement by resveratrol.Scientific reports · 2017Article
- Article
- Targeting the NO/superoxide ratio in adipose tissue: relevance to obesity and diabetes management.British journal of pharmacology · 2017Review
- Acute low-dose endotoxin treatment results in improved whole-body glucose homeostasis in mice.Metabolism: clinical and experimental · 2017Article
- Interplay between the kinin B1 receptor and inducible nitric oxide synthase in insulin resistance.British journal of pharmacology · 2016Article
- miR-628 Promotes Burn-Induced Skeletal Muscle Atrophy via Targeting IRS1.International journal of biological sciences · 2016Article
- Effect of Regular Exercise on Inflammation Induced by Drug-resistant Staphylococcus aureus 3089 in ICR mice.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundIt is believed that the endotoxin lipopolysaccharide (LPS) is implicated in the metabolic perturbations associated with both sepsis and obesity (metabolic endotoxemia). Here we examined the role of inducible nitric oxide synthase (iNOS) in skeletal muscle insulin resistance using LPS challenge in rats and mice as in vivo models of endotoxemia. METHODOLOGY/PRINCIPAL
findingsPharmacological (aminoguanidine) and genetic strategies (iNOS⁻/⁻ mice) were used to counter iNOS induction in vivo. In vitro studies using peroxynitrite (ONOO⁻) or inhibitors of the iNOS pathway, 1400 W and EGCG were conducted in L6 myocytes to determine the mechanism by which iNOS mediates LPS-dependent insulin resistance. In vivo, both pharmacological and genetic invalidation of iNOS prevented LPS-induced muscle insulin resistance. Inhibition of iNOS also prevented insulin resistance in myocytes exposed to cytokine/LPS while exposure of myocytes to ONOO⁻ fully reproduced the inhibitory effect of cytokine/LPS on both insulin-stimulated glucose uptake and PI3K activity. Importantly, LPS treatment in vivo and iNOS induction and ONOO⁻ treatment in vitro promoted tyrosine nitration of IRS-1 and reduced insulin-dependent tyrosine phosphorylation. CONCLUSIONS/SIGNIFICANCE: Our work demonstrates that iNOS-mediated tyrosine nitration of IRS-1 is a key mechanism of skeletal muscle insulin resistance in endotoxemia, and presents nitrosative modification of insulin signaling proteins as a novel therapeutic target for combating muscle insulin resistance in inflammatory settings.
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