Insulin induces alpha1B-adrenergic receptor phosphorylation and desensitization

Life Sci. 2004 Sep 3;75(16):1937-47. doi: 10.1016/j.lfs.2004.03.025.


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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Phosphatidylinositol 4-Kinase / antagonists & inhibitors
  • Androstadienes / metabolism
  • Animals
  • Calcium / metabolism
  • Cells, Cultured
  • Chromatography
  • Chromones / metabolism
  • Cricetinae
  • Dose-Response Relationship, Drug
  • Indoles / metabolism
  • Inositol Phosphates / metabolism
  • Insulin / metabolism
  • Insulin / pharmacology*
  • Maleimides / metabolism
  • Morpholines / metabolism
  • Phosphorylation / drug effects
  • Protein Kinase C / antagonists & inhibitors
  • Rats
  • Receptor, Insulin / metabolism*
  • Receptors, Adrenergic, alpha-1 / metabolism*
  • Staurosporine / metabolism
  • Wortmannin


  • Adra1b protein, rat
  • Androstadienes
  • Chromones
  • Indoles
  • Inositol Phosphates
  • Insulin
  • Maleimides
  • Morpholines
  • Receptors, Adrenergic, alpha-1
  • 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one
  • 1-Phosphatidylinositol 4-Kinase
  • Receptor, Insulin
  • Protein Kinase C
  • Staurosporine
  • bisindolylmaleimide I
  • Calcium
  • Wortmannin