ArticleDiabetes2010
Inducible nitric oxide synthase induction underlies lipid-induced hepatic insulin resistance in mice: potential role of tyrosine nitration of insulin signaling proteins.
Article in Diabetes, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 113 citations in OpenAlex.
- Therapeutic Potential of Flavonoids in Diabetes Mellitus Management: Molecular Insights and the Future Directions for Drug Design.Current drug discovery technologies · 2026Review
- Inducible nitric oxide synthase (iNOS): More than an inducible enzyme? Rethinking the classification of NOS isoforms.Pharmacological research · 2025Review
- Obesity-associated Inflammation and Alloimmunity.Transplantation · 2025Review
- Insulin-like growth factor 1 (IGF-1)-induced changes in cardiac inducible nitric oxide synthase (iNOS) in obese rats.Frontiers in endocrinology · 2025Article
- Article
- High-Fat Diets in Animal Models of Alzheimer's Disease: How Can Eating Too Much Fat Increase Alzheimer's Disease Risk?Journal of Alzheimer's disease : JAD · 2024Review
- Endothelial Dysfunction in Obesity and Therapeutic Targets.Advances in experimental medicine and biology · 2024Review
- Redox regulation in diabetic kidney disease.American journal of physiology. Renal physiology · 2023Review
- iNOS contributes to heart failure with preserved ejection fraction through mitochondrial dysfunction and Akt S-nitrosylation.Journal of advanced research · 2023Article
- Article
- Role of adipose tissue macrophages in obesity-related disorders.The Journal of experimental medicine · 2022Article
- Gut microbiota and fermentation-derived branched chain hydroxy acids mediate health benefits of yogurt consumption in obese mice.Nature communications · 2022Article
- Protective Roles of Apigenin Against Cardiometabolic Diseases: A Systematic Review.Frontiers in nutrition · 2022Review
- Nitrosative Stress and Human Disease: Therapeutic Potential of Denitrosylation.International journal of molecular sciences · 2021Review
- Systemic Insulin Resistance and Metabolic Perturbations in Chow Fed Inducible Nitric Oxide Synthase Knockout Male Mice: Partial Reversal by Nitrite Supplementation.Antioxidants (Basel, Switzerland) · 2020Article
- Mitochondrial uncoupler BAM15 reverses diet-induced obesity and insulin resistance in mice.Nature communications · 2020Article
- Ramipril significantly attenuates the development of non-alcoholic steatohepatitis in hyperlipidaemic rabbits.American journal of cardiovascular disease · 2019Article
- Resilient hepatic mitochondrial function and lack of iNOS dependence in diet-induced insulin resistance.PloS one · 2019Article
- Cytokines promote lipolysis in 3T3-L1 adipocytes through induction of NADPH oxidase 3 expression and superoxide production.Journal of lipid research · 2018Article
- Emerging Roles of Vascular Endothelium in Metabolic Homeostasis.Circulation research · 2018Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe present study was undertaken to assess the contribution of inducible nitric oxide (NO) synthase (iNOS) to lipid-induced insulin resistance in vivo. RESEARCH DESIGN AND
methodsWild-type and iNOS(-/-) mice were infused for 6 h with a 20% intralipid emulsion, during which a hyperinsulinemic-euglycemic clamp was performed.
resultsIn wild-type mice, lipid infusion led to elevated basal hepatic glucose production and marked insulin resistance as revealed by impaired suppression of liver glucose production and reduced peripheral glucose disposal (R(d)) during insulin infusion. Liver insulin resistance was associated with a robust induction of hepatic iNOS, reduced tyrosine phosphorylation of insulin receptor (IR) beta, insulin receptor substrate (IRS)-1, and IRS-2 but elevated serine phosphorylation of IRS proteins as well as decreased Akt activation. The expression of gluconeogenic enzymes Pepck and G6Pc was also increased in the liver of wild-type mice. In contrast to their wild-type counterparts, iNOS(-/-) mice were protected from lipid-induced hepatic and peripheral insulin resistance. Moreover, neither the phosphorylation of insulin signaling intermediates nor expression of gluconeogenic enzymes were altered in the lipid-infused iNOS(-/-) mice compared with their saline-infused controls. Importantly, lipid infusion induced tyrosine nitration of IRbeta, IRS-1, IRS-2, and Akt in wild-type mice but not in iNOS(-/-) animals. Furthermore, tyrosine nitration of hepatic Akt by the NO derivative peroxynitrite blunted insulin-induced Akt tyrosine phosphorylation and kinase activity.
conclusionsThese findings demonstrate that iNOS induction is a novel mechanism by which circulating lipids inhibit hepatic insulin action. Our results further suggest that iNOS may cause hepatic insulin resistance through tyrosine nitration of key insulin signaling proteins.
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