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Protein–protein interaction in insulin signaling and the molecular mechanisms of insulin resistance
Open accessAbstract
Perspective Figure 1 Schematic illustration of major signaling pathways of insulin action.The phosphorylated insulin receptor binds and phosphorylates IRS proteins and Shc, which bind differentially to various downstream signaling proteins.PI3-kinase is critical for metabolic actions of insulin, such as glucose transport, glycogen synthesis, and protein synthesis, whereas Grb-2/SOS complex, which activates the MAP kinase cascade, is critical in mitogenic response.PI3-kinase probably modulates the mitogenic response as well.This series continues from the March 1999, no.6, issue.
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“Inhibitors of PI3K impair glucose transport and block the activation of glycogen synthase and hexokinase- (HK-) II expression [138–146]”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [143]
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“The phosphorylated tyrosine residues of IRS-1 mediate an association with the 85-kDa regulatory subunit of phosphatidylinositol 3-kinase (PI3K), leading to activation of the enzyme [138–140, 143, 144].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [143]
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“The best-studied SH2 proteins that bind to phosphorylated IRS proteins are adaptor molecules, such as the regulatory subunit of PI3K, or the adaptor molecule Grb2 , which associates with son-of-sevenless (SOS) to activate the Ras–MAPK pathway (reviewed in Ref”
BackgroundSelf-citationThe NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance
Vandanmagsar, B., Youm, Y.-H., Ravussin, A., Galgani, J. E., Stadler, K., Mynatt, R. L., Ravussin, E., Stephens, J. M., & Dixit, V. D. (2011) · Nature Medicine · doi:10.1038/nm.2279 · Cited by 2,655
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BackgroundKahn, S. E. (2003) · Diabetologia · doi:10.1007/s00125-002-1009-0 · Cited by 2,166
“Despite tremendous advances in molecular biology and the continued identification of increasingly more molecules involved in the insulin signalling cascade [19], the molecular mechanism(s) that underlies the development of insulin resistance in humans still remains elusive.”
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Metadata
- Authors
- Virkamäki, A., Ueki, K., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Corresponding author
- Kahn, C. Ronald
- Venue
- Journal of Clinical Investigation
- Published
- 1999-04-01
- Volume
- 103
- Issue
- 7
- Pages
- 931-943
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC408269
- OpenAlex
- W2095252238
- Cited by
- 854
- References
- 176
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 15 · 2023: 8 · 2022: 15 · 2021: 12 · 2020: 13 · 2019: 16 · 2018: 13 · 2017: 21 · 2016: 22 · 2015: 26 · 2014: 24 · 2013: 27 · 2012: 31
- FWCI
- 4.88
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- European Foundation for the Study of Diabetes
- National Institutes of Health (DK31036)
- National Institute of Diabetes and Digestive and Kidney Diseases (R37DK031036, DK 33201, R01DK031036, DK45935, DK31036, R01DK045935, R01DK033201)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- insulin signaling, insulin resistance, protein-protein interaction, insulin receptor, Shc, PI3-kinase, MAP kinase cascade, glucose transport, glycogen synthesis, mitogen response
- MeSH terms
- Animals, Humans, Insulin, Insulin Resistance, Phosphorylation, Protein Binding, Receptor, Insulin, Signal Transduction, Gene Targeting, src Homology Domains, Phosphatidylinositol 3-Kinases
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