ArticleProceedings of the National Academy of Sciences of the United States of America2001
A phosphatidylinositol 3-kinase/Akt/mTOR pathway mediates and PTEN antagonizes tumor necrosis factor inhibition of insulin signaling through insulin receptor substrate-1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 157 papers.
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Who cites it
157 citing papers in PubMed, 378 citations in OpenAlex.
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- TNFR1 signaling is positively regulated by Jak-2 and c-Src via tyrosine phosphorylation.Turkish journal of biology = Turk biyoloji dergisi · 2024Article
- Influence of metabolic stress and metformin on synaptic protein profile in SH-SY5Y-derived neurons.Physiological reports · 2023Article
- Smilax china L. Polyphenols Improves Insulin Resistance and Obesity in High-fat Diet-induced Mice Through IRS/AKT-AMPK and NF-κB Signaling Pathways.Plant foods for human nutrition (Dordrecht, Netherlands) · 2023Article
- Metabolic and proteomic signatures of type 2 diabetes subtypes in an Arab population.Nature communications · 2022Article
- Circulating levels of DDIT4 and mTOR, and contributions of BMI, inflammation and insulin sensitivity in hyperlipidemia.Experimental and therapeutic medicine · 2022Article
- The Role of Insulin Receptor Substrate Proteins in Bronchopulmonary Dysplasia and Asthma: New Potential Perspectives.International journal of molecular sciences · 2022Review
- Posttranscriptional Regulation of Insulin Resistance: Implications for Metabolic Diseases.Biomolecules · 2022Review
- Effect of sera from elite athletes on cytokine secretion and insulin signaling in preadipocytes and skeletal muscle cells.Frontiers in molecular biosciences · 2022Article
- Hyperuricemia contributes to glucose intolerance of hepatic inflammatory macrophages and impairs the insulin signaling pathwayFrontiers in immunology · 2022Article
- Hepatocyte-SpecificNutrients · 2021Article
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- Remarkable gastrointestinal and liver manifestations of COVID-19: A clinical and radiologic overview.World journal of clinical cases · 2021Review
- The autophagy protein Becn1 improves insulin sensitivity by promoting adiponectin secretion via exocyst binding.Cell reports · 2021Article
- Molecular regulation of lifespan extension in fertile ant workers.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2021Article
- The possible role of Interleukin-6 as a regulator of insulin sensitivity in patients with neuromyelitis optica spectrum disorder.BMC neurology · 2021Article
97 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Tyrosine phosphorylation of insulin receptor substrate-1 (IRS-1) by the insulin receptor permits this docking protein to interact with signaling proteins that promote insulin action. Serine phosphorylation uncouples IRS-1 from the insulin receptor, thereby inhibiting its tyrosine phosphorylation and insulin signaling. For this reason, there is great interest in identifying serine/threonine kinases for which IRS-1 is a substrate. Tumor necrosis factor (TNF) inhibited insulin-promoted tyrosine phosphorylation of IRS-1 and activated the Akt/protein kinase B serine-threonine kinase, a downstream target for phosphatidylinositol 3-kinase (PI 3-kinase). The effect of TNF on insulin-promoted tyrosine phosphorylation of IRS-1 was blocked by inhibition of PI 3-kinase and the PTEN tumor suppressor, which dephosphorylates the lipids that mediate PI 3-kinase functions, whereas constitutively active Akt impaired insulin-promoted IRS-1 tyrosine phosphorylation. Conversely, TNF inhibition of IRS-1 tyrosine phosphorylation was blocked by kinase dead Akt. Inhibition of IRS-1 tyrosine phosphorylation by TNF was blocked by rapamycin, an inhibitor of the mammalian target of rapamycin (mTOR), a downstream target of Akt. mTOR induced the serine phosphorylation of IRS-1 (Ser-636/639), and such phosphorylation was inhibited by rapamycin. These results suggest that TNF impairs insulin signaling through IRS-1 by activation of a PI 3-kinase/Akt/mTOR pathway, which is antagonized by PTEN.
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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.