Insulin induces alpha1B-adrenergic receptor phosphorylation and desensitization.
The ability of insulin to induce alpha1B-adrenoceptor phosphorylation and desensitization was tested in two model systems: rat-1 cells that stably express alpha1B-adrenoceptors, through transfection, and endogenously express insulin receptors and DDT1 MF2 cells that endogenously express both receptors. Insulin induced concentration-dependent increases in the phosphorylation state of the adrenergic receptors in the two models with similar EC50 values (0.5-2 nM). The effect was rapid in the two systems but it was sustained in rat-1 cells and transient in DDT1 MF2 cells. In both cell lines, the insulin-mediated phosphorylation of alpha1B-adrenoceptors was blocked by wortmannin and LY 294002, and by staurosporine and bisindolylmaleimide I, indicating that the effect involved phosphoinositide 3-kinase and protein kinase C activities. The adrenoceptor phosphorylation induced by insulin was associated to desensitization as evidences by a diminished elevation of intracellular calcium in response to noradrenaline. Inhibitors of phosphoinositide 3-kinase and protein kinase C blocked the functional desensitization induced by insulin.
García-Sáinz
J Adolfo
JA
Instituto de Fisiología Celular, Universidad Nacional Autónoma de México, Apartado Postal 70-248, DF 04510, Mexico. agarcia@ifisiol.unam.mx
Romero-Avila
M Teresa
MT
Molina-Muñoz
Tzindilú
T
Medina
Luz del Carmen
Ldel C
D019870:1-Phosphatidylinositol 4-Kinase / Q000037:antagonists & inhibitors; D000730:Androstadienes / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002478:Cells, Cultured; D002845:Chromatography; D002867:Chromones / Q000378:metabolism; D006224:Cricetinae; D004305:Dose-Response Relationship, Drug; D007211:Indoles / Q000378:metabolism; D007295:Inositol Phosphates / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D008301:Maleimides / Q000378:metabolism; D009025:Morpholines / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D011972:Receptor, Insulin / Q000378:metabolism*; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D019311:Staurosporine / Q000378:metabolism; D000077191:Wortmannin
C547718:Adra1b protein, rat; D000730:Androstadienes; D002867:Chromones; D007211:Indoles; D007295:Inositol Phosphates; D007328:Insulin; D008301:Maleimides; D009025:Morpholines; D018340:Receptors, Adrenergic, alpha-1; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D019870:1-Phosphatidylinositol 4-Kinase; D011972:Receptor, Insulin; D011493:Protein Kinase C; D019311:Staurosporine; C070515:bisindolylmaleimide I; D002118:Calcium; D000077191:Wortmannin