HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 293/6/E1836    most recent 00115.2007v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (14) Citing Articles via Google Scholar Google Scholar Articles by Wu, X. Articles by Goldstein, B. J. Search for Related Content PubMed PubMed Citation Articles by Wu, X. Articles by Goldstein, B. J.

REPORT

Adiponectin suppresses IB kinase activation induced by tumor necrosis factor- or high glucose in endothelial cells: role of cAMP and AMP kinase signaling

Division of Endocrinology, Diabetes, and Metabolic Diseases, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania

Submitted 20 February 2007 ; accepted in final form 5 October 2007

Adiponectin is a protein secreted from adipocytes that exhibits salutary effects in the vascular endothelium by signaling mechanisms that are not well understood. In obesity-related disease states and type 2 diabetes, circulating substances, including tumor necrosis factor- (TNF) and high glucose, activate IB kinase (IKK)β and reduce the abundance of its substrate, inhibitor of B (IB), leading to nuclear translocation of the transcription factor NF-B and stimulation of an inflammatory signaling cascade closely associated with endothelial dysfunction. The present study demonstrates that the globular domain of adiponectin (gAd) potently suppresses the activation of IKKβ by either TNF or high glucose in human umbilical vein endothelial cells and ameliorates the associated loss of IB protein. Interestingly, activation of AMP kinase was substantially more effective than cAMP signaling in suppressing high glucose-induced IKKβ activity, whereas both pathways were comparably active in suppressing the TNF-induced increase in IKKβ. Both cAMP/protein kinase A signaling and activation of the AMP kinase pathway played a role in the suppression by gAd of TNF- and high glucose-mediated IKKβ activation. These findings support an important role for adiponectin in anti-inflammatory signaling in the endothelium and also imply that multiple pathways are involved in the cellular effects of adiponectin.

inflammation; endothelial dysfunction; insulin resistance; NF-B

This article has been cited by other articles:

				D.-E. Lee, S. Kehlenbrink, H. Lee, M. Hawkins, and J. S. Yudkin Getting the message across: mechanisms of physiological cross talk by adipose tissue Am J Physiol Endocrinol Metab, June 1, 2009; 296(6): E1210 - E1229. [Abstract] [Full Text] [PDF]

				K. Kawauchi, K. Araki, K. Tobiume, and N. Tanaka Loss of p53 enhances catalytic activity of IKK{beta} through O-linked {beta}-N-acetyl glucosamine modification PNAS, March 3, 2009; 106(9): 3431 - 3436. [Abstract] [Full Text] [PDF]

				N. Anderson and J. Borlak Molecular Mechanisms and Therapeutic Targets in Steatosis and Steatohepatitis Pharmacol. Rev., September 1, 2008; 60(3): 311 - 357. [Abstract] [Full Text] [PDF]

				J. Chung, A.-K. Nguyen, D. C. Henstridge, A. G. Holmes, M. H. S. Chan, J. L. Mesa, G. I. Lancaster, R. J. Southgate, C. R. Bruce, S. J. Duffy, et al. HSP72 protects against obesity-induced insulin resistance PNAS, February 5, 2008; 105(5): 1739 - 1744. [Abstract] [Full Text] [PDF]