Effect of glucagon on insulin receptor substrate-1 (IRS-1) phosphorylation and association with phosphatidylinositol 3-kinase (PI 3-kinase)

FEBS Lett. 1995 Aug 14;370(1-2):131-4. doi: 10.1016/0014-5793(95)00809-n.

Abstract

In the present study we have examined the levels and phosphorylation state of the insulin receptor and insulin receptor substrate 1 (IRS-1) as well as the association between IRS-1 and phosphatidylinositol 3-kinase (PI 3-kinase) in the liver and muscle of rats treated with glucagon. There was a decrease in the insulin-stimulated receptor and IRS-1 phosphorylation levels which was paralleled by a reduced association between IRS-1 and PI 3-kinase in vivo in the liver and muscle of glucagon-treated rats. These observations suggest that glucagon, probably acting through cAMP, may impair insulin signaling in the three early steps in insulin action after binding.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Glucagon / pharmacology*
  • Insulin / pharmacology*
  • Insulin Receptor Substrate Proteins
  • Liver / drug effects
  • Liver / metabolism*
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism*
  • Phosphatidylinositol 3-Kinases
  • Phosphoproteins / drug effects
  • Phosphoproteins / isolation & purification
  • Phosphoproteins / metabolism*
  • Phosphorylation
  • Phosphotransferases (Alcohol Group Acceptor) / drug effects
  • Phosphotransferases (Alcohol Group Acceptor) / metabolism*
  • Phosphotyrosine
  • Rats
  • Reference Values
  • Tyrosine / analogs & derivatives
  • Tyrosine / metabolism

Substances

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