Insulin‐mediated sensitization of adenylyl cyclase activation

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Abstract
1 Insulin may be an important regulator of vascular function. We have previously studied lymphocyte β-adrenoceptors as a model for the human vascular β-adrenoceptor. To examine the effects of insulin on human β-adrenoceptor responsiveness, adenylyl cyclase activity, cyclic AMP-dependent protein kinase activity and β-adrenoceptor radioligand binding assays were performed on permeabilized mononuclear leukocytes. 2 With acute exposure to insulin in vitro, followed by washing and permeabilization there was a dose-dependent increase in both lymphocyte NaF-stimulated activity and β-adrenoceptor-stimulated adenylyl cyclase activity paralleling an increase in β-adrenoceptor-stimulated protein kinase A activity. Manganese-, forskolin- and forskolin plus guanylimidodiphosphate-stimulated adenylyl cyclase activities were not altered by insulin pretreatment. Additionally, mononulcear leukocyte β-adrenoceptor density, proportion of externalized receptors and receptor affinity for agonist were not altered. 3 The data indicate that acute exposure to insulin sensitizes G-protein-stimulated adenylyl cyclase activity. These findings suggest a potential role for insulin in the regulation of β-adrenoceptor responsiveness in man.