Effect of insulin levels on the phosphorylation of specific amino acid residues in IRS-1: Implications for burn-induced insulin resistance

  • Authors:
    • Xiao-Ming Lu
    • Victoria F. Hamrahi
    • Ronald G. Tompkins
    • Alan J. Fischman
  • View Affiliations

  • Published online on: October 1, 2009     https://doi.org/10.3892/ijmm_00000262
  • Pages: 531-538
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Abstract

Alterations in the phosphorylation and/or degradation of insulin receptor substrate-1 (IRS-1) produced by burn injury may be responsible, at least in part, for burn-induced insulin resistance. In particular, following burn injury, reductions in glucose uptake by skeletal muscle may be secondary to altered abundance and/or phosphorylation of IRS-1. In this study, we performed in vitro experiments with 293 cells transfected with IRS-1. These studies demonstrated that there is a dramatic change in the phosphorylation pattern of Tyr, Ser and Thr residues in IRS-1 as a function of insulin levels. Specifically, Ser and Thr residues in the C-terminal region were phosphorylated only at high insulin levels. SILAC (stable isotope labeling with amino acids in cell culture) followed by sequencing of C-terminal IRS-1 fragments by tandem mass spectrometry demonstrated that there is significant protein cleavage at these sites. These findings suggest that one of the biological roles of the C-terminal region of IRS-1 may be negative modulation of the finely coordinated insulin signaling system. Clearly, this could represent an important factor in insulin resistance, and identification of kinase inhibitors that are responsible for the phosphorylation may foster new lines of research for the development of drugs for treating insulin resistance.

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October 2009
Volume 24 Issue 4

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Lu X, Hamrahi VF, Tompkins RG and Fischman AJ: Effect of insulin levels on the phosphorylation of specific amino acid residues in IRS-1: Implications for burn-induced insulin resistance. Int J Mol Med 24: 531-538, 2009
APA
Lu, X., Hamrahi, V.F., Tompkins, R.G., & Fischman, A.J. (2009). Effect of insulin levels on the phosphorylation of specific amino acid residues in IRS-1: Implications for burn-induced insulin resistance. International Journal of Molecular Medicine, 24, 531-538. https://doi.org/10.3892/ijmm_00000262
MLA
Lu, X., Hamrahi, V. F., Tompkins, R. G., Fischman, A. J."Effect of insulin levels on the phosphorylation of specific amino acid residues in IRS-1: Implications for burn-induced insulin resistance". International Journal of Molecular Medicine 24.4 (2009): 531-538.
Chicago
Lu, X., Hamrahi, V. F., Tompkins, R. G., Fischman, A. J."Effect of insulin levels on the phosphorylation of specific amino acid residues in IRS-1: Implications for burn-induced insulin resistance". International Journal of Molecular Medicine 24, no. 4 (2009): 531-538. https://doi.org/10.3892/ijmm_00000262