Effect of actinomycin and insulin on the metabolism of isolated rat diaphragm

The postulation that RNA synthesis is the molecular site of action of insulin was tested by examining the effect of actinomycin on the response of isolated rat diaphragm muscle to the hormone. Actinomycin markedly suppressed, but did not completely inhibit, nucleic acid synthesis in muscle; the effect of the antibiotic on protein synthesis was not nearly as great. Actinomycin treatment of diaphragm muscle did not prevent the insulin stimulation of protein synthesis, of glucose uptake, or of aminoisobutyric acid accumulation; nor, for that matter, did it prevent the influence of the hormone to increase incorporation of [¹⁴C₈]adenine into nucleic acids. The results do not lend comfort to the theory that an effect of insulin on the synthesis of messenger RNA is fundamental to its action, although it does not rule out that possibility with certainty.