Role of hormone-sensitive low Km cAMP phosphodiesterase in regulation of cAMP-dependent protein kinase and lipolysis in rat adipocytes.
The time-courses of isoproterenol activation of rat adipocyte particulate low Km cAMP phosphodiesterase (PDE) activity, cAMP-dependent protein kinase (A-kinase), and glycerol production were measured in the presence and absence of insulin. Isoproterenol (100 nM) alone rapidly activated A-kinase 8- to 10-fold and increased particulate cAMP PDE by approximately 100%. A-kinase and PDE activity remained relatively constant for at least 25 to 30 min. Kact values for isoproterenol activation of PDE and lipolysis were similar. In comparison with isoproterenol, insulin (0.1-0.3 nM) alone increased particulate cAMP PDE at a slower rate and to a lesser extent (by approximately 50% within 12 to 16 min) and without any change in A-kinase. With insulin plus isoproterenol there was a rapid, transient, and synergistic activation of particulate cAMP PDE, which temporally correlated with a decrease in A-kinase and reduction in lipolysis. These and other data suggest the following: 1) there is a close concentration-dependent and temporal relationship in isoproterenol activation of adenylate cyclase, of A-kinase, and of particulate cAMP PDE; 2) isoproterenol and insulin activate particulate cAMP PDE by two distinct mechanisms; 3) the temporal changes in PDE and A-kinase in the presence of insulin and isoproterenol suggest that insulin activation of the PDE does not require, but may be enhanced by, elevated cAMP and is important in the antilipolytic action of insulin.
Smith
C J
CJ
Laboratory of Cellular Metabolism, National Heart, Lung, and Blood Institute, Bethesda, Maryland 20892.
Manganiello
V C
VC
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000032:analysis / Q000502:physiology*; D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008066:Lipolysis / Q000187:drug effects; D008297:Male; D011494:Protein Kinases / Q000032:analysis*; D051381:Rats; D011919:Rats, Inbred Strains
D007328:Insulin; D011494:Protein Kinases; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D007545:Isoproterenol