The Antilipolytic Action of Insulin on Adrenocorticotrophin-Stimulated Rat Adipocytes

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Abstract
The extent to which a fall in cellular cyclic AMP could account for the antilipolytic action in rat epididymal adipocytes incubated with adrenocorticotrophic hormone was studied. The antilipolytic effect, measured by suppression of glycerol release, was always associated with a decrease in cyclic AMP, but the magnitude of the fall was modified by several factors. For example, it was greater when the cAMP level was high, as when it is at its peak after hormone stimulation, or when cell concentrations are low. Glucose did not modify appreciably the insulin effect on the nucleotide level. The inhibitory effects of insulin on corticotrophin-stimulated lipolysis and cyclic AMP levels were detectable at the concentrations of 1 microU/ml and were biphasic, with maximal effects at 10-100 microU/ml. Protein kinase activity ratio was similarly affected. Activity of cyclic-AMP-dependent protein kinase conformed closely to the level of cyclic AMP. There was no indication that insulin modified the sensitivity of the kinase to cyclic AMP. Insulin did not alter the relationship of cellular cyclic AMP levels to glycerol when adipocytes were incubated with various concentrations of corticotrophin. This was true, irrespective of whether measurements were made when cyclic AMP was on the upward rise after hormone stimulation, or on the decline. The curves obtained with and without insulin were superimposable. It is concluded that the inhibitory action of insulin on lipolysis in fat cells can be fully accounted for by a decrease in cyclic AMP.