AJP - Cell Physiology, Vol 270, Issue 2 C562-C569, Copyright © 1996 by American Physiological Society
Insulin sensitizes beta-agonist and forskolin-stimulated lipolysis to inhibition by 2',5'-dideoxyadenosine
Y. Gokmen-Polar, E. C. Coronel, S. W. Bahouth and J. N. Fain
Department of Biochemistry, University of Tennessee, Memphis 38163, USA.
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.
