화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.402, No.3, 455-460, 2010
Extracellular high dosages of adenosine triphosphate induce inflammatory response and insulin resistance in rat adipocytes
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 1 mM We then observed that ATP dose-dependently reduced the level of 1 kappa B. 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 I kappa B 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 (C) 2010 Elsevier Inc All rights reserved