help button home button Endocrine Society Endocrinology
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology, doi:10.1210/en.2004-0524
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ma, Y.
Right arrow Articles by Messina, J. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ma, Y.
Right arrow Articles by Messina, J. L.
Endocrinology Vol. 145, No. 11 5168-5176
Copyright © 2004 by The Endocrine Society

Mechanisms of Hemorrhage-Induced Hepatic Insulin Resistance: Role of Tumor Necrosis Factor-{alpha}

Yuchen Ma, Balazs Toth, Adam B. Keeton, LaWanda T. Holland, Irshad H. Chaudry and Joseph L. Messina

Department of Pathology (Y.M., A.B.K., L.T.H., J.L.M.), Division of Molecular and Cellular Pathology, and Center for Surgical Research and Department of Surgery (B.T., I.H.C.), The University of Alabama at Birmingham, Birmingham Alabama 35294

Address all correspondence and requests for reprints to: Joseph L. Messina, Ph.D., Department of Pathology, Division of Molecular and Cellular Pathology, Volker Hall, G019, 1670 University Boulevard, University of Alabama at Birmingham, Birmingham, Alabama 35294-0019. E-mail: messina{at}path.uab.edu.

Hemorrhage, sepsis, burn injury, surgical trauma and critical illness all induce insulin resistance. Recently we found that trauma and hemorrhage acutely induced hepatic insulin resistance in the rat. However, the mechanisms of this hemorrhage-induced acute hepatic insulin resistance are unknown. Here we report on the mechanisms of this hepatic insulin resistance. Protein levels and phosphorylation of the insulin receptor and insulin receptor substrate-1/2 (IRS-1/2) were measured, as was the association between IRS-1/2 and phosphatidylinositol 3-kinase (PI3K). Also examined were the hepatic expression of TNF{alpha} and TNF{alpha}-induced serine phosphorylation of IRS-1. Insulin receptor and IRS-1/2 protein levels and insulin-induced tyrosine phosphorylation of the insulin receptor were unaltered. In contrast, insulin-induced tyrosine phosphorylation of IRS-1/2 and association between IRS-1/2 and PI3K were dramatically reduced after hemorrhage. Hepatic levels of TNF{alpha} mRNA and protein were increased as was phosphorylation of IRS-1 serine 307 after hemorrhage. Our data provide the first evidence that compromised IRS-1/2 tyrosine phosphorylation and their association with PI3K contribute to hemorrhage-induced acute hepatic insulin resistance. Increased local TNF{alpha} may play a role in inducing this hepatic insulin resistance after trauma and hemorrhage.




This article has been cited by other articles:


Home page
 J EndocrinolHome page
L. Zhai and J. L Messina
Age and tissue specific differences in the development of acute insulin resistance following injury
J. Endocrinol., December 1, 2009; 203(3): 365 - 374.
[Abstract] [Full Text] [PDF]

Home page
 J Intensive Care MedHome page
N. T. Mowery, M. J. Dortch, L. A. Dossett, P. R. Norris, J. J. Diaz Jr, J. A. Morris Jr, and A. K. May
Review of a Large Clinical Series: Insulin Resistance Despite Tight Glucose Control Is Associated With Mortality in Critically Ill Surgical Patients
J Intensive Care Med, July 1, 2009; 24(4): 242 - 251.
[Abstract] [PDF]

Home page
 EndocrinologyHome page
L. Li, L. H. Thompson, L. Zhao, and J. L. Messina
Tissue-Specific Difference in the Molecular Mechanisms for the Development of Acute Insulin Resistance after Injury
Endocrinology, January 1, 2009; 150(1): 24 - 32.
[Abstract] [Full Text] [PDF]

Home page
 EndocrinologyHome page
J. Xu, H. T. Kim, Y. Ma, L. Zhao, L. Zhai, N. Kokorina, P. Wang, and J. L. Messina
Trauma and Hemorrhage-Induced Acute Hepatic Insulin Resistance: Dominant Role of Tumor Necrosis Factor-{alpha}
Endocrinology, May 1, 2008; 149(5): 2369 - 2382.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
L. Langouche, S. Vander Perre, P. J. Wouters, A. D'Hoore, T. K. Hansen, and G. Van den Berghe
Effect of Intensive Insulin Therapy on Insulin Sensitivity in the Critically Ill
J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 3890 - 3897.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Physiol. Regul. Integr. Comp. Physiol.Home page
M. Wang, P. R. Crisostomo, C. Herring, K. K. Meldrum, and D. R. Meldrum
Human progenitor cells from bone marrow or adipose tissue produce VEGF, HGF, and IGF-I in response to TNF by a p38 MAPK-dependent mechanism
Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2006; 291(4): R880 - R884.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
I. Bergheim, J. P. Luyendyk, C. Steele, G. K. Russell, L. Guo, R. A. Roth, and G. E. Arteel
Metformin Prevents Endotoxin-Induced Liver Injury after Partial Hepatectomy
J. Pharmacol. Exp. Ther., March 1, 2006; 316(3): 1053 - 1061.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals
Copyright © 2004 by The Endocrine Society