REGULATION OF CARDIAC INSULIN-RECEPTOR FUNCTION BY GUANOSINE NUCLEOTIDES

The present study examined the effect of [S-35]GTP on the function of insulin receptors partially purified from adult rat cardiomyocytes by WGA chromatography. [S-35]GTP increased receptor autophosphorylation about two times and fully mimicked the stimulatory action of insulin on poly(Glu:Tyr) phosphorylation with no additional effect of the hormone. The effect of [S-35]GTP was specific, dose-dependent, and due to an increase in the V(max) of the kinase. In the presence of ATP or AMP-PNP. insulin significantly enhanced the binding of [S-35]GTP to the partially purified insulin receptor. The findings suggest coupling of the insulin receptor to a G-protein which may be involved in the regulation of tyrosine kinase activity.