Insulin stimulation of cyclic AMP phosphodiesterase is independent from the G-protein pathways involved in adenylate cyclase regulation.
The intact rat adipocyte was used to investigate the possibility of common intermediates in the insulin stimulation of cyclic AMP phosphodiesterase and the beta-adrenergic/adenosine regulation of adenylate cyclase. A five minute incubation of the isolated adipocytes with insulin produced a 50-100% increase in the phosphodiesterase activity found in the particulate fraction of homogenates. The insulin stimulation was not impaired by the presence of either agonist or antagonists of the inhibitory adenosine receptor which acts on adenylate cyclase. Phosphodiesterase activation by insulin was also observable above the level of stimulation produced by the beta-adrenergic agent isoproterenol and forskolin. The validity of the enzyme activity measurements was supported by measurements of the hormonal actions on cyclic AMP levels within the cells. Possible crossover between the adenylate cyclase and phosphodiesterase regulation systems at a post-receptor site was investigated using adipocytes exposed to bacterial toxins specific for the modification of guanine nucleotide binding proteins. Both cholera toxin, which irreversibly activates Gs and pertussis toxin which inactivates Gi caused some stimulation of the phosphodiesterase activity and suppressed activation by isoproterenol, but neither toxin prevented the insulin stimulation of cyclic AMP phosphodiesterase. These results suggest, while common components may participate in the beta-adrenergic stimulation of both adenylate cyclase and phosphodiesterase, the mechanism of insulin activation of the phosphodiesterase does not involve the components of adenylate cyclase regulation.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000378:metabolism*; D000243:Adenosine Deaminase / Q000494:pharmacology; D037361:Adenylate Cyclase Toxin; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D002772:Cholera Toxin / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000502:physiology*; D007328:Insulin / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D037342:Pertussis Toxin; D010660:Phenylisopropyladenosine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D037361:Adenylate Cyclase Toxin; D007328:Insulin; D010566:Virulence Factors, Bordetella; D005576:Colforsin; D010660:Phenylisopropyladenosine; D002772:Cholera Toxin; D000242:Cyclic AMP; D037342:Pertussis Toxin; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D000243:Adenosine Deaminase; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D007545:Isoproterenol