Tyrosine kinase activity of skeletal muscle-derived insulin receptors isolated from rats that had undergone euglycemic clamps at various insulin infusion rates was examined. Receptors were isolated under conditions designed to preserve their in vivo phosphorylation state, and their kinase activity toward histone was measured in the absence of in vitro exposure to insulin. Results showed that significant activation of the insulin-receptor kinase occurred after exposure in vivo to mean serum insulin concentrations as low as 34 ± 3.5 μU/ml and that maximal activation was achieved by insulin levels ≤2000 μU/ml. There was a highly significant correlation between receptor kinase activity and serum insulin concentration in the physiologic range (r = .92, P < .0001) and between kinase activity and glucose utilization rate (r = .74, P < .0001). These findings further support a role for the insulin-receptor kinase in insulin action in vivo, and this model provides a novel method for the study of the effect of factors known to influence insulin action on the insulin-receptor kinase under physiologic conditions.

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