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Biochem Biophys Res Commun. 2010 Nov 19;402(3):455-60. doi: 10.1016/j.bbrc.2010.10.028. Epub 2010 Oct 12.

Extracellular high dosages of adenosine triphosphate induce inflammatory response and insulin resistance in rat adipocytes.

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  • 1Dept. of Nutrition, School of Public Health, Sun Yat-Sen University, Guangzhou, People's Republic of China.


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.

Copyright © 2010 Elsevier Inc. All rights reserved.

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