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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“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]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Adipose Expression of Tumor Necrosis Factor-α: Direct Role in Obesity-Linked Insulin Resistance
Hotamisligil, G. S., Shargill, N. S., & Spiegelman, B. M. (1993) · Science · doi:10.1126/science.7678183 · Cited by 7,518
Hotamisligil, G. S., Arner, P., Caro, J. F., Atkinson, R. L., & Spiegelman, B. M. (1995) · Journal of Clinical Investigation · doi:10.1172/jci117936 · Cited by 3,543
A central role for JNK in obesity and insulin resistance
Hirosumi, J., Tuncman, G., Chang, L., Görgün, C. Z., Uysal, K. T., Maeda, K., Karin, M., & Hotamisligil, G. S. (2002) · Nature · doi:10.1038/nature01137 · Cited by 3,359
Hotamisligil, G. S., Peraldi, P., Budavari, A., Ellis, R., White, M. F., & Spiegelman, B. M. (1996) · Science · doi:10.1126/science.271.5249.665 · Cited by 2,630
Yudkin, J. S., Stehouwer, C. D. A., Emeis, J. J., & Coppack, S. W. (1999) · Arteriosclerosis, Thrombosis, and Vascular Biology · doi:10.1161/01.atv.19.4.972 · Cited by 2,465
Elchebly, M., Payette, P., Michaliszyn, E., Cromlish, W., Collins, S., Loy, A. L., Normandin, D., Cheng, A., Himms-Hagen, J., Chan, C.-C., et al. (1999) · Science · doi:10.1126/science.283.5407.1544 · Cited by 2,210
Stamler, J. S., Simon, D. I., Osborne, J. A., Mullins, M. E., Jaraki, O., Michel, T. M., Singel, D. J., & Loscalzo, J. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.1.444 · Cited by 1,471
Tumor Necrosis Factor α: A Key Component of the Obesity-Diabetes Link
Hotamışlıgil, G. S., & Spiegelman, B. M. (1994) · Diabetes · doi:10.2337/diab.43.11.1271 · Cited by 1,353
Lipotoxic heart disease in obese rats: Implications for human obesity
Zhou, Y.-T., Grayburn, P., Karim, A., Shimabukuro, M., Higa, M., Baetens, D., Orci, L., & Unger, R. H. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.4.1784 · Cited by 1,265
Stamler (2001) · doi:10.1016/s0092-8674(01)00495-0 · Cited by 1,261
Klaman, L. D., Boss, O., Peroni, O. D., Kim, J. K., Martino, J. L., Zabolotny, J. M., Moghal, N., Lubkin, M., Kim, Y.-B., Sharpe, A. H., et al. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.15.5479-5489.2000 · Cited by 1,235
Fatty acid-induced β cell apoptosis: A link between obesity and diabetes
Shimabukuro, M., Zhou, Y.-T., Levi, M., & Unger, R. H. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.5.2498 · Cited by 1,142
Nitric Oxide: Pathophysiological Mechanisms
Gross, S. S., & Wolin, M. S. (1995) · Annual Review of Physiology · doi:10.1146/annurev.ph.57.030195.003513 · Cited by 888
The Biotin Switch Method for the Detection of S -Nitrosylated Proteins
Jaffrey, S. R., & Snyder, S. H. (2001) · Science Signaling · doi:10.1126/stke.2001.86.pl1 · Cited by 855
S -Nitrosylation of Parkin Regulates Ubiquitination and Compromises Parkin's Protective Function
Chung, K. K. K., Thomas, B., Li, X., Pletniková, O., Troncoso, J. C., Marsh, L., Dawson, V. L., & Dawson, T. M. (2004) · Science · doi:10.1126/science.1093891 · Cited by 772
(S)NO Signals: Translocation, Regulation, and a Consensus Motif
Stamler, J. S., Toone, E. J., Lipton, S. A., & Sucher, N. J. (1997) · Neuron · doi:10.1016/s0896-6273(00)80310-4 · Cited by 679
Perreault, M., & Marette, A. (2001) · Nature Medicine · doi:10.1038/nm1001-1138 · Cited by 550
Bonora, E., Moghetti, P., Zancanaro, C., CIGOLINI, M., Querena, M., Cacciatori, V., Corgnati, A., & Muggeo, M. (1989) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem-68-2-374 · Cited by 528
Leighton, B., & Cooper, G. J. S. (1988) · Nature · doi:10.1038/335632a0 · Cited by 473
Storlien, L. H., James, D. E., Burleigh, K. M., Chisholm, D. J., & Kraegen, E. W. (1986) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1986.251.5.e576 · Cited by 458
Nitric Oxide Regulates Exocytosis by S-Nitrosylation of N-ethylmaleimide-Sensitive Factor
Matsushita, K., Morrell, C. N., Cambien, B., Yang, S.-X., Yamakuchi, M., Bao, C., Hara, M. R., Quick, R. A., Cao, W., O'Rourke, B. P., et al. (2003) · Cell · doi:10.1016/s0092-8674(03)00803-1 · Cited by 446
Peraldi, P., Hotamisligil, G. S., Buurman, W. A., White, M. F., & Spiegelman, B. M. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.22.13018 · Cited by 412
Vedia, L. M. Y., McDonald, B. R., Reep, B. R., Brüne, B., Silvio, M. D., Billiar, T. R., & Lapetina, E. G. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)73985-4 · Cited by 390
Li, M., Pascual, G., & Glass, C. K. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.13.4699-4707.2000 · Cited by 377
Nitric oxide-stimulated guanine nucleotide exchange on p21ras
Lander, H. M., Ogiste, J. S., Pearce, S. F. A., Levi, R., & Novogrodsky, A. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.13.7017 · Cited by 364
Tumor necrosis factor alpha: a key component of the obesity-diabetes link
Hotamışlıgil, G. S., & Spiegelman, B. M. (1994) · Diabetes · doi:10.2337/diabetes.43.11.1271 · Cited by 354
Saad, M. J., Folli, F., Kahn, J. A., & Kahn, C. R. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116803 · Cited by 349
Self-citationSaad, M. J. A., Araki, E., Miralpeix, M., Rothenberg, P., White, M. F., & Kahn, C. R. (1992) · Journal of Clinical Investigation · doi:10.1172/jci116060 · Cited by 321
Self-citationInsulin resistance in soleus muscle from obese Zucker rats. Involvement of several defective sites
Crettaz, M., Prentki, M., Zaninetti, D., & Jeanrenaud, B. (1980) · Biochemical Journal · doi:10.1042/bj1860525 · Cited by 311
De Fea, K., & Roth, R. A. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.50.31400 · Cited by 298
Basal and Stimulated Protein S-Nitrosylation in Multiple Cell Types and Tissues
Gow, A. J., Chen, Q., Hess, D. T., Day, B. J., Ischiropoulos, H., & Stamler, J. S. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.c100746200 · Cited by 294
Role of nitric oxide in obesity-induced beta cell disease.
Shimabukuro, M., Ohneda, M., Lee, Y., & Unger, R. H. (1997) · Journal of Clinical Investigation · doi:10.1172/jci119534 · Cited by 282
Kapur, S., Bédard, S., Marcotte, B., Côté, C. H., & Marette, A. (1997) · Diabetes · doi:10.2337/diab.46.11.1691 · Cited by 225 · cited 3×
“It is well established that proinflammatory cytokines (tumor necrosis factor- and interleukin-6) and endotoxins synergistically increase NO production via increased expression of iNOS in rat skeletal muscle and cultured myocytes and adipocytes (8,17,18).”
BackgroundDirect and indirect effects of nitric oxide in chemical reactions relevant to biology
Wink, D. A., Grisham, M. B., Mitchell, J. B., & Ford, P. C. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)68006-9 · Cited by 182
Determination of nitric oxide using fluorescence spectroscopy
Miles, A. M., Wink, D. A., Cook, J. C., & Grisham, M. B. (1996) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/s0076-6879(96)68013-6 · Cited by 177
BÉDARD, S., Marcotte, B., & Marette, A. (1997) · Biochemical Journal · doi:10.1042/bj3250487 · Cited by 175
Broillet, M.-C., & Firestein, S. (1996) · Neuron · doi:10.1016/s0896-6273(00)80055-0 · Cited by 158
de Oliveira, M. G., Shishido, S. M., Seabra, A. B., & Morgon, N. H. (2002) · The Journal of Physical Chemistry A · doi:10.1021/jp025756u · Cited by 138
Self-citationCeddia, R. B., William, W., & Curi, R. A. (1999) · International Journal of Obesity · doi:10.1038/sj.ijo.0800762 · Cited by 132
Self-citationInducible nitric oxide synthase plays a role in LPS-induced hyperglycemia and insulin resistance
Sugita, H., Kaneki, M., Tokunaga, E., Sugita, M., Koike, C., Yasuhara, S., Tompkins, R. G., & Martyn, J. A. J. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00087.2001 · Cited by 130
Maggi, L. B., Sadeghi, H., Weigand, C. M., Scarim, A. L., Heitmeier, M. R., & Corbett, J. A. (2000) · Diabetes · doi:10.2337/diabetes.49.3.346 · Cited by 128
Regulation of β cell glucokinase by S-nitrosylation and association with nitric oxide synthase
Rizzo, M. A., & Piston, D. W. (2003) · The Journal of Cell Biology · doi:10.1083/jcb.200301063 · Cited by 123
Detection and proteomic identification of S-nitrosylated proteins in endothelial cells
Martı́nez-Ruiz, A., & Lamas, S. (2004) · Archives of Biochemistry and Biophysics · doi:10.1016/j.abb.2003.12.006 · Cited by 120
Park, H.-S., Park, E., Kim, M.-S., Ahn, K., Kim, I. Y., & Choi, E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.275.4.2527 · Cited by 119
Insulin Induces Tyrosine Phosphorylation of JAK2 in Insulin-sensitive Tissues of the Intact Rat
Saad, M. J. A., Carvalho, C. R. D. O., Thirone, A. C. P., & Velloso, L. A. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.36.22100 · Cited by 107
Self-citationCell signaling by nitric oxide.
Lane, P. B., & Gross, S. S. (1999) · PubMed · Cited by 103
Regulation of protein tyrosine phosphatase 1B in intact cells by S-nitrosothiols
Li, S., & Whorton, A. R. (2003) · Archives of Biochemistry and Biophysics · doi:10.1016/s0003-9861(02)00696-3 · Cited by 99
Chin, J. E., Liu, F., & Roth, R. A. (1994) · Molecular Endocrinology · doi:10.1210/mend.8.1.7512195 · Cited by 90
Kwon, G., Xu, G. H., Marshall, C. A., & McDaniel, M. L. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.26.18702 · Cited by 80
Mechanism of adipose tissue iNOS induction in endotoxemia
Kapur, S., Marcotte, B., & Marette, A. (1999) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1999.276.4.e635 · Cited by 78
Zecchin, H. G., Bezerra, R. M. N., Carvalheira, J. B. C., Carvalho-Filho, M. A., Metze, K., Franchini, K. G., & Saad, M. J. A. (2003) · Diabetologia · doi:10.1007/s00125-003-1073-0 · Cited by 65
Self-citationKapur, S., Bedard, S., Marcotte, B., et al. (1997) · Diabetes · doi:10.2337/diabetes.46.11.1691 · Cited by 56
Complementation Mapping in Microcell Hybrids: Localization of XRCC4 to 5q15–q21
Athwal, R. S., & Kaur, G. P. (1996) · Methods · doi:10.1006/meth.1996.0003 · Cited by 29
Cited by
Sorted by citations
Inflammation and insulin resistance
de Luca, C., & Olefsky, J. M. (2008) · FEBS Letters · doi:10.1016/j.febslet.2007.11.057 · Cited by 1,161
Trends in insulin resistance: insights into mechanisms and therapeutic strategy
Li, M., Chi, X., Wang, Y., Setrerrahmane, S., Xie, W., & Xu, H. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01073-0 · Cited by 939
Molecular mechanisms of ROS production and oxidative stress in diabetes
Newsholme, P., Cruzat, V. F., Keane, K. N., Carlessi, R., & de Bittencourt, P. I. H. (2016) · Biochemical Journal · doi:10.1042/bcj20160503c · Cited by 878
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
Self-citationRetractedSelenium biochemistry and its role for human health
Roman, M., Jitaru, P., & Barbante, C. (2014) · Metallomics · doi:10.1039/c3mt00185g · Cited by 823
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
