title: Propranolol improves impaired hepatic phosphatidylinositol 3-kinase/akt signaling after burn injury.
abstract: 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.
authors.affiliation: Department of Biochemistry and Molecular Biology, University of Texas Medical Branch, Galveston, Texas, United States of America.
authors.forename: Natasha C
authors.initials: NC
authors.lastname: Brooks
authors.forename: Juquan
authors.initials: J
authors.lastname: Song
authors.forename: Darren
authors.initials: D
authors.lastname: Boehning
authors.forename: Robert
authors.initials: R
authors.lastname: Kraft
authors.forename: Celeste C
authors.initials: CC
authors.lastname: Finnerty
authors.forename: David N
authors.initials: DN
authors.lastname: Herndon
authors.forename: Marc G
authors.initials: MG
authors.lastname: Jeschke
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002056:Burns / Q000201:enzymology*; D059865:Endoplasmic Reticulum Stress / Q000187:drug effects; D007328:Insulin / Q000378:metabolism; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008099:Liver / Q000201:enzymology*; D008297:Male; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D000319:Adrenergic beta-Antagonists; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D011433:Propranolol; D058539:Phosphatidylinositol 3-Kinase; D051057:Proto-Oncogene Proteins c-akt; D048031:JNK Mitogen-Activated Protein Kinases