title: Cellular cyclic AMP levels modulate insulin sensitivity and responsiveness--evidence against a significant role of Gi in insulin signal transduction.
abstract: Treating rats with pertussis toxin (PTX) both elevated the adipocyte cAMP levels and impaired sensitivity and responsiveness to the antilipolytic effect of insulin in the presence of different beta-adrenergic agonists. However, in the presence of a fixed medium concentration of the degradable cAMP analogue, 8-bromo-cAMP, the effect of insulin was similar in PTX- and control cells. Elevating the cAMP levels in control cells either through different concentrations of the cAMP analogue or addition of adenosine deaminase impaired both insulin sensitivity and responsiveness to a similar extent as that seen in PTX-treated cells. The antilipolytic effect of insulin was exerted through the activation of the cGMP-inhibitable phosphodiesterase (cGI-PDE) as it was dose-dependently impaired by the specific cGI-PDE inhibitor OPC 3911. The results show the importance of the cellular cAMP levels in modulating insulin sensitivity and action. Gi plays a minor role, if any, for the signal transduction of the antilipolytic effect of insulin.
authors.affiliation: Department of Medicine, University of Göteborg, Sahlgren's Hospital, Göteborg, Sweden.
authors.forename: C
authors.initials: C
authors.lastname: Wesslau
authors.forename: J W
authors.initials: JW
authors.lastname: Eriksson
authors.forename: U
authors.initials: U
authors.lastname: Smith
mesh_terms: D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D004822:Epididymis; D019204:GTP-Binding Proteins / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism* / Q000494:pharmacology; D008066:Lipolysis / Q000502:physiology*; D008297:Male; D037342:Pertussis Toxin; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D007328:Insulin; D010726:Phosphodiesterase Inhibitors; D015363:Quinolones; D010566:Virulence Factors, Bordetella; D015124:8-Bromo Cyclic Adenosine Monophosphate; C060853:OPC 3911; D000242:Cyclic AMP; D037342:Pertussis Toxin; D019204:GTP-Binding Proteins