Propranolol improves impaired hepatic phosphatidylinositol 3-kinase/akt signaling after burn injury

Mol Med. 2012 May 9;18(1):707-11. doi: 10.2119/molmed.2011.00277.


Severe burn injury is associated with induction of the hepatic endoplasmic reticulum (ER) stress response. ER stress leads to activation of c-Jun N-terminal kinase (JNK), suppression of insulin receptor signaling via phosphorylation of insulin receptor substrate 1 and subsequent insulin resistance. Marked and sustained increases in catecholamines are prominent after a burn. Here, we show that administration of propranolol, a nonselective β1/2 adrenergic receptor antagonist, attenuates ER stress and JNK activation. Attenuation of ER stress by propranolol results in increased insulin sensitivity, as determined by activation of hepatic phosphatidylinositol 3-kinase and Akt. We conclude that catecholamine release is responsible for the ER stress response and impaired insulin receptor signaling after burn injury.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology*
  • Animals
  • Burns / enzymology*
  • Endoplasmic Reticulum Stress / drug effects
  • Insulin / metabolism
  • Insulin Receptor Substrate Proteins / metabolism
  • JNK Mitogen-Activated Protein Kinases / metabolism
  • Liver / enzymology*
  • Male
  • Phosphatidylinositol 3-Kinase / metabolism*
  • Phosphorylation / drug effects
  • Propranolol / pharmacology*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction / drug effects*


  • Adrenergic beta-Antagonists
  • Insulin
  • Insulin Receptor Substrate Proteins
  • Propranolol
  • Phosphatidylinositol 3-Kinase
  • Proto-Oncogene Proteins c-akt
  • JNK Mitogen-Activated Protein Kinases