Document Detail


Extracellular high dosages of adenosine triphosphate induce inflammatory response and insulin resistance in rat adipocytes.
MedLine Citation:
PMID:  20946888     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Adenosine triphosphate (ATP), an important signaling molecule, participates in various pathophysiological processes via the activation of purinergic-receptors. Recent studies have shown that the expression and function of purinergic-receptors (P2-receptors) could be altered in diabetic or hyperinsulinemia conditions. To characterize the effect of ATP on insulin signaling, we treated primary rat adipocytes with varied concentrations of ATP. The pre-treatment led to impaired insulin signaling, i.e., blunted phosphorylation in Insulin Receptor Substrate-1 (IRS-1) tyrosine and Protein Kinase B (PKB) Ser473 in response to insulin treatment, when ATP concentration reached 1mM. We then observed that ATP dose-dependently reduced the level of IκB, a negative regulator of inflammatory response. Consistently, IRS-1 Ser307 phosphorylation in response to insulin treatment, a site for inflammatory pathway to interfere insulin signaling, was enhanced by ATP. Furthermore, effects of ATP on insulin signaling and IκB content were blocked by P2-receptor inhibition. Finally, insulin-stimulated glucose uptake was impaired by ATP in adipocytes but not in the L6 muscle cells. This study therefore shows for the first time the involvement of ATP-evoked P2-receptor activation in mediating the inflammatory response and the generation of insulin resistance in adipocytes.
Authors:
Zhiwen Yu; Tianru Jin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-10-12
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  402     ISSN:  1090-2104     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2010-12-28     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  455-60     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Inc. All rights reserved.
Affiliation:
Dept. of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China.
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / metabolism,  pharmacology*
Adipocytes / drug effects*,  metabolism
Animals
Cells, Cultured
Glucose / metabolism*
Inflammation / chemically induced*,  metabolism
Insulin / metabolism*
Insulin Receptor Substrate Proteins / metabolism
Insulin Resistance*
Male
Phosphorylation
Rats
Rats, Sprague-Dawley
Serine / metabolism
Signal Transduction / drug effects
Chemical
Reg. No./Substance:
0/Insulin Receptor Substrate Proteins; 0/Irs1 protein, rat; 11061-68-0/Insulin; 50-99-7/Glucose; 56-45-1/Serine; 56-65-5/Adenosine Triphosphate

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