title: Cyclic AMP impairs the rapid effect of insulin to enhance cell-surface insulin-binding capacity in rat adipocytes.
abstract: The aim of this study was to characterize further the interaction between cyclic AMP (cAMP) and insulin binding and action. Rat adipocytes were preincubated at 37 degrees C for 20 min, and after energy depletion with KCN, cell-surface 125I-insulin binding was measured. As recently reported [Eriksson, Lönnroth & Smith (1992) Diabetes 41, 707-714], preincubation with insulin rapidly increased the number of cell-surface insulin binding sites up to approximately 5-fold through recruitment within the plasma membrane. This was completely abolished by the presence of 4 mM-N6-monobutyryl cAMP (a non-hydrolysable cAMP analogue) or 1 microM-isoprenaline, without any apparent change in receptor internalization. Insulin-stimulated receptor tyrosine kinase activity was attenuated by the cAMP analogue only if the exposure of the adipocytes was prolonged to 60 min. The cellular sensitivity to insulin, assessed as 3-O-methylglucose uptake, was markedly decreased by the cAMP analogue, and this could be attributed to the impaired cell-surface binding. However, evidence for post-receptor interactions between cAMP and insulin was also found: an impairment of maximal insulin-stimulated 3-O-methylglucose transport and a delay in the rate of activation of the glucose transport system by insulin. In conclusion, these data demonstrate that beta-adrenergic stimulation and elevated cAMP levels markedly impair the ability of insulin to enhance cell-surface insulin-binding capacity. This novel interaction may be an important mechanism for the cellular insensitivity to insulin produced by cAMP.
authors.affiliation: Department of Medicine II, University of Gothenburg, Sahlgren's Hospital, Sweden.
authors.forename: J W
authors.initials: JW
authors.lastname: Eriksson
authors.forename: P
authors.initials: P
authors.lastname: Lönnroth
authors.forename: U
authors.initials: U
authors.lastname: Smith
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000502:physiology*; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D007328:Insulin; D008757:Methylglucosides; D000242:Cyclic AMP; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin