The DOI matches its Crossref record; 53 of the 53 references it cites were found in a registry or an index.
S-Nitrosation of the Insulin Receptor, Insulin Receptor Substrate 1, and Protein Kinase B/Akt
Open accessAbstract
Evidence demonstrates that exogenous nitric oxide (NO) and the NO produced by inducible nitric oxide synthase (iNOS) can induce insulin resistance in muscle. Here, we investigated whether this insulin resistance could be mediated by S-nitrosation of proteins involved in early steps of the insulin signal transduction pathway. Exogenous NO donated by S-nitrosoglutathione (GSNO) induced in vitro and in vivo S-nitrosation of the insulin receptor beta subunit (IRbeta) and protein kinase B/Akt (Akt) and reduced their kinase activity in muscle. Insulin receptor substrate (IRS)-1 was also rapidly S-nitrosated, and its expression was reduced after chronic GSNO treatment. In two distinct models of insulin resistance associated with enhanced iNOS expression-diet-induced obesity and the ob/ob diabetic mice-we observed enhanced S-nitrosation of IRbeta/IRS-1 and Akt in muscle. Reversal of S-nitrosation of these proteins by reducing iNOS expression yielded an improvement in insulin action in both animal models. Thus, S-nitrosation of proteins involved in insulin signal transduction is a novel molecular mechanism of iNOS-induced insulin resistance.
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“Although ablation of the NOS2 gene has no effect on weight gain, its absence was shown to improve glucose tolerance, normalize insulin sensitivity, and prevent derangements in PI3K/Akt signaling in high fat-fed mice [346].”
From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [346]
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Cites
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Tsukumo, D. M. L., Carvalho-Filho, M. A., Carvalheira, J. B. C., Prada, P. O., Hirabara, S. M., Schenka, A. A., Araújo, E. P., Vassallo, J., Curi, R., Velloso, L. A., et al. (2007) · Diabetes · doi:10.2337/db06-1595 · Cited by 826
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Metadata
- Authors
- Carvalho-Filho, M. A., Ueno, M., Hirabara, S. M., Seabra, A. B., Carvalheira, J. B. C., de Oliveira, M. G., Velloso, L. A., Curi, R., & Saad, M. J. A.
- Affiliations
- Department of Internal Medicine, State University of Campinas, UNICAMP, Campinas, Brazil
- Universidade Estadual de Campinas (UNICAMP) (BR)
- Universidade de São Paulo (BR)
- Chemistry Institute, State University of Campinas, UNICAMP, Campinas, Brazil
- Venue
- Diabetes
- Publisher
- American Diabetes Association
- Published
- 2005-04-01
- Volume
- 54
- Issue
- 4
- Pages
- 959-967
- ISSN
- 0012-1797 (ISSN-L)
- 1939-327X
- OpenAlex
- W2144153442
- Cited by
- 277
- References
- 53
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 3 · 2023: 5 · 2022: 15 · 2021: 5 · 2020: 13 · 2019: 9 · 2018: 12 · 2017: 13 · 2016: 13 · 2015: 22 · 2014: 13 · 2013: 18 · 2012: 25
- FWCI
- 7.59
- Type
- journal article
- Language
- en
- Update notices
- expression_of_concern (2023-10-23)
- Open access
- bronze
- doi.org
- Locations
- Diabetes (publishedVersion)
- PubMed (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (publishedVersion)
- University of Groningen research database (University of Groningen / Centre for Information Technology) (submittedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Keywords
- S-nitrosylation, insulin resistance, insulin receptor beta-subunit, IRS-1, Akt/protein kinase B, nitric oxide, inducible nitric oxide synthase, S-nitrosoglutathione, insulin signaling, skeletal muscle, diet-induced obesity, ob/ob mice, kinase activity
- MeSH terms
- Rosiglitazone, Animals, Glutathione, Insulin, Insulin Resistance, Male, Nitric Oxide, Nitro Compounds, Obesity, Phosphoproteins, Protein Processing, Post-Translational, Proto-Oncogene Proteins, Receptor, Insulin, Nitrosation, Mice, Inbred NOD, Rats, Wistar, Protein Serine-Threonine Kinases, Muscle, Skeletal, Thiazolidinediones, Proto-Oncogene Proteins c-akt, Mice, Rats, Insulin Receptor Substrate Proteins
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