Ethanol impairs insulin receptor substrate-1 mediated signal transduction during rat liver regeneration

Biochem Biophys Res Commun. 1994 Feb 28;199(1):403-9. doi: 10.1006/bbrc.1994.1243.


Chronic ethanol exposure inhibits the capacity of the liver to regenerate. Insulin is a potent hepatotrophic factor and it was determined if ethanol interferes with insulin receptor substrate (IRS-1)-protein mediated signal transduction during liver regeneration. Tyrosyl phosphorylation of IRS-1 was strikingly increased prior to the major wave of DNA synthesis in isocaloric pair-fed control rats; a blunted and delayed response was found in ethanol-fed rats. Enzymatic activity of phosphatidylinositol 3-kinase, a Src homology 2 (SH2) domain containing signal transduction molecule was enhanced by the association with tyrosyl phosphorylated IRS-1, whereas in ethanol-fed rats, this activity was greatly diminished and delayed. These results indicate that one potential molecular mechanism whereby ethanol inhibits hepatocyte DNA synthesis is through its action on the IRS-1-mediated signal transduction cascade.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Ethanol / pharmacology*
  • Female
  • Insulin Receptor Substrate Proteins
  • Liver Regeneration / drug effects*
  • Phosphatidylinositol 3-Kinases
  • Phosphoproteins / metabolism*
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism
  • Phosphotyrosine
  • Rats
  • Signal Transduction / drug effects
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism


  • Insulin Receptor Substrate Proteins
  • Irs1 protein, rat
  • Phosphoproteins
  • Phosphotyrosine
  • Ethanol
  • Tyrosine
  • Phosphatidylinositol 3-Kinases
  • Phosphotransferases (Alcohol Group Acceptor)