In isolated rat adipocytes stimulated with theophylline (1 mmol/l), pyrazinoylguanidine (PZG) downregulated both lipolysis and cyclic AMP concentrations, raising the possibility that PZG stimulates adipose insulin-sensitive phosphodiesterase. To investigate this directly, we measured PZG's effects on phosphodiesterase activity in rat adipocytes. PZG (10 mumol/l) as well as insulin (0.1-1 mU) increased adipose phosphodiesterase activity, whereas theophylline reduced it. Also investigated were PZG's effects on gluconeogenesis and cyclic AMP in perfused rat liver where PZG decreased gluconeogenesis and cyclic AMP concentrations.
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