Angiotensin II induces tyrosine phosphorylation of insulin receptor substrate 1 and its association with phosphatidylinositol 3-kinase in rat heart.

摘要: We have investigated whether angiotensin II (AII) is able to induce insulin receptor substrate 1 (IRS-1) phosphorylation and its association with phosphatidylinositol 3-kinase (PI 3-kinase) in the rat heart vivo. The state of IRS-1 following infusion or AII via vena cava was assessed after immunoprecipitation an anti-peptide antibody followed by immunoblotting anti-phosphotyrosine anti-PI antibody. Densitometry indicated a 5.6 +/- 1.3-fold increase stimulation 12.8 3.1-fold insulin. effect maximal at concentration 10(-8) M occurred min infusion. There also 6.1 1.2-fold IRS-1-associated PI response AII. In isolated perfused result similar, showing direct on this pathway. When animals were pretreated for h DuP 753, non-peptide AII-receptor (AT1 receptor) antagonist, there marked reduction AII-induced tyrosine IRS-1, suggesting that initially mediated AT1 receptor. conclude stimulates 3-kinase. This pathway thus represents additional signalling mechanism stimulated