Insulin-mediated sensitization of adenylyl cyclase activation.
1. Insulin may be an important regulator of vascular function. We have previously studied lymphocyte beta-adrenoceptors as a model for the human vascular beta-adrenoceptor. To examine the effects of insulin on human beta-adrenoceptor responsiveness, adenylyl cyclase activity, cyclic AMP-dependent protein kinase activity and beta-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 beta-adrenoceptor-stimulated adenylyl cyclase activity paralleling an increase in beta-adrenoceptor-stimulated protein kinase A activity. Manganese-, forskolin- and forskolin plus guanylimidodiphosphate-stimulated adenylyl cyclase activities were not altered by insulin pretreatment. Additionally, mononuclear leukocyte beta-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 beta-adrenoceptor responsiveness in man.
Feldman
R D
RD
Department of Medicine, University of Western Ontario, Canada.
D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism; D000328:Adult; D005576:Colforsin / Q000494:pharmacology; D006165:Guanylyl Imidodiphosphate / Q000494:pharmacology; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D011943:Receptors, Adrenergic, beta / Q000032:analysis / Q000187:drug effects
D007328:Insulin; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D006165:Guanylyl Imidodiphosphate; D000262:Adenylyl Cyclases