INSULIN SENSITIZES BETA-AGONIST AND FORSKOLIN-STIMULATED LIPOLYSIS TOINHIBITION 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)-catechola mine agonists and forskolin without affecting their stimulation of lip olysis. 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 cellul ar compartments distinct from those involved in the regulation of bulk protein kinase A activity. However, there was a good correlation betw een effects of lipolytic agents on cytosolic protein kinase A activity in fat cell extracts and Lipolysis. Furthermore, it was possible to s ee an inhibition of the increase due to beta-agonists in cAMP accumula tion, protein kinase A activity, and lipolysis by 2',5'-dideoxyadenosi ne in the presence of insulin. These data suggest that the readily mea surable accumulation of cAMP seen with catecholamines in the absence o f insulin is in a compartment separate from that involved in protein k inase A activation.