Activation of cyclic AMP phosphodiesterase by phorbol and protein kinase C pathway.
Insulin (INS) stimulates, and diabetes inhibits, low Km cAMP phosphodiesterase (PDE). This mechanism, at least in part, accounts for the lowering of cyclic AMP levels in plasma and tissue of diabetic patients and animals. Phorbol, a tumor-promoting agent known to act through protein kinase C and calcium translocation, exhibits a powerful effect stimulating PDE in rat adipose tissue. Nifedipine, a calcium channel blocker, inhibits insulin, but not phorbol stimulated PDE. These data demonstrate new effects of inositide diacylglycerol-Ca++ pathway components on PDE and suggest some common pathways of activation of low Km cAMP PDE through insulin and phorbol esters.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D010704:Phorbols / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*
D007328:Insulin; D010704:Phorbols; D011493:Protein Kinase C; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D009543:Nifedipine; D013755:Tetradecanoylphorbol Acetate