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 witho ut OPC 3911, a specific inhibitor of cGI-PDE, and 3-O-methylglucose up take was measured. Insulin-stimulated glucose transport was impaired b y OPC 3911 (similar to 15%) and this impairment became more pronounced in the presence of the degradable cAMP-analogue 8-bromo-cAMP (similar to 45%). This analogue alone did not significantly decrease glucose t ransport. Furthermore, insulin sensitivity was impaired by the combina tion 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-P DE exerts a modulating effect on the stimulatory action of insulin on glucose transport. This effect is particularly pronounced when the cel lular cAMP levels are elevated.