An assessment of the ability of insulin-stimulated cyclic AMP phosphodiesterase to decrease hepatocyte intracellular cyclic AMP concentrations

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Abstract
Treatment of hepatocytes with either NH4Cl (10 mM) or fructose (10 mM) blocks insulin''s activation of the dense-vesicle cAMP phosphodiesterase. The ability of insulin (10 nM) to decrease intracellular cAMP concentrations raised by glucagon (10 nM) was unaffected by pre-treatment with either NH4Cl (10 mM) or fructose (10 mM). The dense-vesicle enzyme probably does not play a significant role in this action of insulin; as yet unidentified cAMP phosphodiesterase(s) must be activated by insulin. Treatment of hepatocytes with either NH4Cl or fructose appeared to increase, reversibly, cAMP phosphodiesterase activity. When N6-(phenylisopropyl)adenosine was used to prevent glucagon from blocking insulin''s activation of the plasma-membrane cAMP phosphodiesterase activity, insulin''s ability to decrease intracellular cAMP concentrations in glucagon-treated hepatocytes was increased markedly. Insulin''s activation of the plasma-membrane cAMP phosphodiesterase activity can exert a potent effect in decreasing intracellular cAMP concentrations elevated by glucagon.