Adenosine modulates insulin activation of insulin receptor kinase in intact rat adipocytes

Endogenous adenosine enhances the insulin sensitivity of isolated rat adipocytes. We studied whether this effect was related to an ability of adenosine to alter the activation of insulin receptor kinase by insulin. It was found that depletion of endogenous adenosine by adenosine deaminase treatment decreases insulin's ability to activate the receptor kinase at submaximal insulin concentrations. This occurred without changes in insulin binding. At 4 ng/ml insulin, adenosine deaminase decreased insulin activation of insulin receptor kinase by 25%, a reduction that equalled the effect of adenosine deaminase on insulin stimulation of 2-deoxyglucose transport. The effects of adenosine deaminase on both insulin activation of insulin receptor kinase and insulin stimulation of 2-deoxyglucose transport were reversed by the addition of N6-phenylisopropyl-adenosine, a nonhydrolyzable adenosine analog. Our data are consistent with the view that adenosine modulates the coupling of insulin binding to biological actions of insulin at or before the level of activation of insulin receptor kinase.