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IRS-1-Mediated Inhibition of Insulin Receptor Tyrosine Kinase Activity in TNF-α- and Obesity-Induced Insulin Resistance
Results indicate that TNF-α induces insulin resistance through an unexpected action of IRS-1 to attenuate insulin receptor signaling. Expand
Mechanism by Which Fatty Acids Inhibit Insulin Activation of Insulin Receptor Substrate-1 (IRS-1)-associated Phosphatidylinositol 3-Kinase Activity in Muscle*
The hypothesis that an increase in plasma fatty acid concentration results in a increase in intracellular fatty acyl-CoA and DAG concentrations, which results in activation of PKC-θ leading to increased IRS-1 Ser307 phosphorylation is supported. Expand
Disruption of IRS-2 causes type 2 diabetes in mice
It is shown that disruption of IRS-2 impairs both peripheral insulin signalling and pancreatic β-cell function, indicating that dysfunction of IRS-2 may contribute to the pathophysiology of human type 2 diabetes. Expand
IRS proteins and the common path to diabetes.
  • M. White
  • Biology, Medicine
  • American journal of physiology. Endocrinology and…
  • 1 September 2002
The broad role of IRS-1 and IRS-2 in cell growth and survival reveals a common regulatory pathway linking development, somatic growth, fertility, neuronal proliferation, and aging to the core mechanisms used by vertebrates for nutrient sensing. Expand
The insulin signaling system.
  • M. White, C. Kahn
  • Medicine, Biology
  • The Journal of biological chemistry
  • 7 January 1994
Phosphorylation of Ser307 in Insulin Receptor Substrate-1 Blocks Interactions with the Insulin Receptor and Inhibits Insulin Action*
In 32D myeloid progenitor cells, phosphorylation of Ser307 inhibited insulin stimulation of the phosphatidylinositol 3-kinase and MAPK cascades, suggesting that inhibition of PTB domain function in IRS-1 by phosphorylated Ser307 might be a general mechanism to regulate insulin signaling. Expand
Structure of the insulin receptor substrate IRS-1 defines a unique signal transduction protein
During insulin stimulation, the IRS-1 protein undergoes tyrosine phosphorylation and binds phosphatidylinositol 3-kinase, suggesting that IRS–1 acts as a multisite Mocking' protein to bind signal-transducing molecules containing Src-homology 2 and SRC-Homology-3 domains, which may link the insulin receptor kinase and enzymes regulating cellular growth and metabolism. Expand
The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growth.
It is proposed that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts. Expand
SOCS-1 and SOCS-3 Block Insulin Signaling by Ubiquitin-mediated Degradation of IRS1 and IRS2*
SOCS-mediated degradation of IRS proteins, presumably via the elongin BC ubiquitin-ligase, might be a general mechanism of inflammation-induced insulin resistance, providing a target for therapy. Expand
Role of IRS-2 in insulin and cytokine signalling
The discovery of a second IRS-signalling protein, IRS-2, which is expressed in many cells, including tissues from IRS-1 −/− mice, and may be essential for signalling by several receptor systems, is provisionally resolved. Expand