Controle of the metabolism and lipolytic effects of cyclic 3',5'-adenosine monophosphate in adipose tissue by insulin, methyl xanthines, and nicotinic acid.

1. We have tested the hypothesis that insulin might decrease the levels of cyclic AMP (CAMP) in rat epididymal adipose tissue by stimulating the activity of a CAMP phosphodiesterase. 2. Dibutyryl cyclic AMP (DBcAMP) was comparable to CAMP as a substrate for CAMP phosphodiesterase of adipose tissue; the hydrolysis of both cyclic nucleotides was inhibited by theophylline. 3. DBcAMP, but not CAMP, was strongly lipolytic in free adipose cells; this activity was unaffected by insulin in vitro at concentrations of the hormone sufficient to be strongly antilipolytic against epinephrine. DBcAMP-stimulated lipolysis was inhibited by nicotinic acid, a stimulator of CAMP phosphodiesterase. 4. Lipolytic concentrations of theophylline and caffeine synergistically stimulated the lipolytic effect of DBcAMP in free adipose cells at all but saturating levels of DBcAMP. Lower, nonlipolytic concentrations of the methyl xanthines also stimulated the lipolytic activity of DBcAMP, and this synergism was reversed by insulin, but only at low concentrations of the cyclic nucleotide. 5. Neither prior treatment of fat pads with insulin nor the presence of insulin during enzyme assay affected the CAMP phosphodiesterase activities of 2000 x g sediment and supernatant fractions. 6. Neither hyponor hyperinsulinism in donor rats influenced the CAMP phosphodiesterase activity of adipose tissue.