The hypothesis that the effects of insulin on adipose tissue metabolism are secondary to inhibition of cyclic AMP accumulation was investigated using isolated rat white fat cells. No effect of incubation with insulin on the subsequent adenyl cyclase activity of fat cell ghosts or on phosphodiesterase activity of the high speed supernatant from homogenates of white fat cells was seen. Under conditions in which insulin inhibited the lipolytic action of catecholamines it did not affect the accumulation of total cyclic AMP, labeled cyclic AMP or ATP in white fat cells. The stimulation of leucine incorporation into protein and of [1-14C] glucose oxidation by insulin was abolished by high concentrations of theophylline. However, in the presence of an amount of norepinephrine which gave a 75 per cent maximal stimulation of lipolysis the increase in leucine incorporation into protein and glucose oxidation due to insulin was actually enhanced. The addition of theophylline to cells incubated with norepinephrine abolished the antilipolytic and other actions of insulin. The addition of dibutyryl cyclic AMP or fatty acids mimicked the effects of lipolytic agents on insulin action except that fatty acids stimulated lactate formation. The inhibition by high concentrations of lipolytic agents on the stimulation by insulin of glucose metabolism and leucine incorporation into protein appears to be due to accumulation of intracellular free fatty acids. Our results suggest that the antilipolytic action of insulin may also be unrelated to effects of insulin on cyclic AMP accumulation.

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