The cGMP-inhibitable phosphodiesterase modulates glucose transport activation by insulin.
To assess the role of the cGMP-inhibitable phosphodiesterase (cGI-PDE) in the action of insulin on glucose transport, adipocytes from young, lean rats were preincubated for 20 min at 37 degrees C with and without OPC 3911, a specific inhibitor of cGI-PDE, and 3-O-methylglucose uptake was measured. Insulin-stimulated glucose transport was impaired by OPC 3911 (approximately 15%) and this impairment became more pronounced in the presence of the degradable cAMP-analogue 8-bromo-cAMP (approximately 45%). This analogue alone did not significantly decrease glucose transport. Furthermore, insulin sensitivity was impaired by the combination of OPC 3911 and 8-bromo-cAMP. Maximal insulin-stimulated glucose transport in adipocytes from aging, obese rats was affected similarly by OPC 3911 and 8-bromo-cAMP, suggesting that cGI-PDE activity is not markedly altered in this insulin-resistant state. In conclusion, cGI-PDE exerts a modulating effect on the stimulatory action of insulin on glucose transport. This effect is particularly pronounced when the cellular cAMP levels are elevated.
Eriksson
J W
JW
Department of Medicine, University of Göteborg, Sahlgren's Hospital, Sweden.
Wesslau
C
C
Smith
U
U
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D017667:Adipocytes / Q000187:drug effects*; D000367:Age Factors; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D000242:Cyclic AMP / Q000378:metabolism; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D015363:Quinolones / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D007328:Insulin; D010726:Phosphodiesterase Inhibitors; D015363:Quinolones; D015124:8-Bromo Cyclic Adenosine Monophosphate; C060853:OPC 3911; D000242:Cyclic AMP; D005947:Glucose