Comprehensive effect of norepinephrine and angiotensin Ⅱ on the tyrosine phosphorylation of insulin receptor and insulin receptor substance 1 in rat cardiac cells

Objective: To investigate the comprehensive effects of norepinephrine(NE) and angiotensin Ⅱ(AngⅡ) on tyrosine phosphorylation of insulin receptor β(Ins-Rβ) subunit and insulin receptor substance 1(IRS-1) in rat cardiac cells,and the mechanism of insulin resistance.Methods: The myocardial cells from the neonatal rat(1 to 3d) were primary cultured,and co-cultured with the same concentration of the mixture of NE and AngⅡ for 72 h according to the concentration gradient.The protein expressions of insulin signal molecules were detected using Western blotting.Losartan,Ang Ⅱ receptor blockers,was added into each experiment group,and the independent effect of NE and AngⅡ was observed.Results: Under the same concentration of the mixture of NE and Ang Ⅱ,the protein expression levels of Ins-R,IRS-1 and glucose transporter type 4(GLUT4),and level of tyrosine phosphorylation of Ins-Rβ decreased,and the level of tyrosine phosphorylation of IRS-1 increased in myocardial cells(P<0.05).The effect of 1 μmol/L of losartan on the level of tyrosine phosphorylation of Ins-Rβ was not obvious(P>0.05),which could decrease the level of tyrosine phosphorylation of IRS-1(P<0.05).Conclusions: The same concentration of the mixture of NE and AngⅡ can decrease the tyrosine phosphorylation level of Ins-R β subunit,and increase the tyrosine phosphorylation level of IRS-1.NE is the crucial factor in decreasing the tyrosine phosphorylation level of Ins-Rβ,and the AngⅡ is the crucial factor in increasing the tyrosine phosphorylation level of IRS-1.