Insulin sensitizes beta-agonist and forskolin-stimulated lipolysis to inhibition by 2',5'-dideoxyadenosine.
In isolated rat adipocytes incubated in the absence of insulin, 2',5'-dideoxyadenosine blocked the increase in total adenosine 3',5'-cyclic monophosphate (cAMP) accumulation due to beta 1- or beta 3-catecholamine agonists and forskolin without affecting their stimulation of lipolysis. The inhibition of cAMP accumulation by 2',5'-dideoxyadenosine was not reflected in the total cytosolic cAMP-dependent protein kinase A activity, suggesting that the inhibition of cAMP occurred in cellular compartments distinct from those involved in the regulation of bulk protein kinase A activity. However, there was a good correlation between effects of lipolytic agents on cytosolic protein kinase A activity in fat cell extracts and lipolysis. Furthermore, it was possible to see an inhibition of the increase due to beta-agonists in cAMP accumulation, protein kinase A activity, and lipolysis by 2',5'-dideoxyadenosine in the presence of insulin. These data suggest that the readily measurable accumulation of cAMP seen with catecholamines in the absence of insulin is in a compartment separate from that involved in protein kinase A activation.
Gokmen-Polar
Y
Y
Department of Biochemistry, University of Tennessee, Memphis 38163, USA.
Coronel
E C
EC
Bahouth
S W
SW
Fain
J N
JN
D017667:Adipocytes / Q000378:metabolism; D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000818:Animals; D002395:Catecholamines / Q000819:agonists; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000037:antagonists & inhibitors / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D016048:Dideoxyadenosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004149:Dioxoles / Q000494:pharmacology; D004357:Drug Synergism; D007328:Insulin / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley
D000318:Adrenergic beta-Agonists; D002395:Catecholamines; D004149:Dioxoles; D007328:Insulin; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D005576:Colforsin; D016048:Dideoxyadenosine; C021008:2',5'-dideoxyadenosine; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases