Effect of glucagon on insulin receptor substrate‐1 (IRS‐1) phosphorylation and association with phosphatidylinositol 3‐kinase (PI 3‐kinase)

In the present study we have examined the levels and phosphorylation state of the insulin receptor and insulin receptor substrate 1 (IRS‐1) as well as the association between IRS‐1 and phosphatidylinositol 3‐kinase (PI 3‐kinase) in the liver and muscle of rats treated with glucagon. There was a decrease in the insulin‐stimulated receptor and IRS‐1 phosphorylation levels which was paralleled by a reduced association between IRS‐1 and PI 3‐kinase in vivo in the liver and muscle of glucagon‐treated rats. These observations suggest that glucagon, probably acting through cAMP, may impair insulin signaling in the three early steps in insulin action after binding.