Hemorrhage, sepsis, burn injury, surgical trauma and critical illness all induce insulin resistance. Recently we found that trauma and hemorrhage acutely induced hepatic insulin resistance in the rat. However, the mechanisms of this hemorrhage-induced acute hepatic insulin resistance are unknown. Here we report on the mechanisms of this hepatic insulin resistance. Protein levels and phosphoryla...

Liberman Z, Plotkin B, Tennenbaum T, Eldar-Finkelman H. Coordinated phosphorylation of insulin receptor substrate-1 by glycogen synthase kinase-3 and protein kinase C II in the diabetic fat tissue. Am J Physiol Endocrinol Metab 294: E1169–E1177, 2008. First published April 22, 2008; doi:10.1152/ajpendo.00050.2008.— Serine/threonine phosphorylation of insulin receptor substrate-1 (IRS-1) is an i...

Insulin resistance in metabolic syndrome subjects is profound in spite of muscle insulin receptor and insulin-responsive glucose transporter (GLUT4) expression being nearly normal. Insulin receptor tyrosine kinase phosphorylation of insulin receptor substrate-1 (IRS-1) at Tyr896 is a necessary step in insulin stimulation of translocation of GLUT4 to the cell surface. Serine phosphorylation of I...

Imaging polarimetry of the 850 km continuum emission in the NGC 7538 region, obtained with the SCUBA Polarimeter, is presented. The polarization map is interpreted in terms of thermal radiation by magnetically aligned dust grains. Two prominent cores associated with IRS 1 and IRS 11, IRS 1(SMM), and IRS 11(SMM), are found in the surface brightness map. Although these cores look similar in surfa...

Vascular permeability factor/vascular endothelial growth factor (VPF/VEGF), the critical molecule in tumor angiogenesis, is regulated by different stimuli, such as hypoxia and oncogenes, and also by growth factors. Previously we have shown that in AsPC-1 pancreatic adenocarcinoma cells, insulin-like growth factor receptor (IGF-IR) regulates VPF/VEGF expression. Insulin receptor substrate-1 and ...

The 60 kDa insulin receptor substrate in rat adipocytes that binds to the PI-3 kinase displays several functional characteristics in common with the IRS proteins; so we propose the name pp60(IRS3) to distinguish it from other tyrosine phosphorylated proteins of similar size. During insulin stimulation, p85 associated with pp60(IRS3) more rapidly than with IRS-1 or IRS-2. In mice lacking IRS-1, ...

S6K1 has emerged as a critical signaling component in the development of insulin resistance through phosphorylation and inhibition of IRS-1 function. This effect can be triggered directly by nutrients such as amino acids or by insulin through a homeostatic negative-feedback loop. However, the role of S6K1 in mediating IRS-1 phosphorylation in a physiological setting of nutrient overload is unre...

BACKGROUND/AIMS Insulin receptor (IR-alpha and IR-beta) is reduced in the kidney of insulin-resistant rodents. It is unknown if there are also reductions in insulin receptor substrate (IRS)-1 or if these effects are due to metabolic injury. Thereby, we hypothesized intrinsically high aerobic fitness would protect against high-fat diet (HFD)-induced reactive oxygen species (ROS) and IRS-1 degrad...

Although originating from a human breast cancer, BT-20 cells do not form colonies in soft agar. BT-20 cells do not express insulin receptor substrate-1 (IRS-1), which is known to promote both normal and abnormal growth and to inhibit differentiation. Stable expression of IRS-1 confers to BT-20 cells the ability to form colonies in soft agar. BT-20 cells form tumors in xenografts in mice, but th...