TY - JOUR
T1 - Propranolol improves impaired hepatic phosphatidylinositol 3-kinase/akt signaling after burn injury.
AU - Brooks, Natasha C.
AU - Song, Juquan
AU - Boehning, Darren
AU - Kraft, Robert
AU - Finnerty, Celeste C.
AU - Herndon, David
AU - Jeschke, Marc G.
N1 - Funding Information:
The authors would like to thank Paul McKeever for his technical assistance, in addition to Alexandra Smith and Yaeko Hiyama for critically reading the manuscript. This work was supported by grants from Shriners Hospitals for Children (SHG 8660 and 6840), the National Institutes of Health (R01-GM087285-0182, R01-GM56687 and P50-GM60338), CFI Leader’s Opportunity Fund (Project 25407) and the Physicians’ Services Incorporated Foundation, Health Research Grant Program.
PY - 2012
Y1 - 2012
N2 - 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.
AB - 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.
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U2 - 10.2119/molmed.2011.00277
DO - 10.2119/molmed.2011.00277
M3 - Article
C2 - 22396018
AN - SCOPUS:84871087875
SN - 1076-1551
VL - 18
SP - 707
EP - 711
JO - Molecular medicine (Cambridge, Mass.)
JF - Molecular medicine (Cambridge, Mass.)
ER -