Article révisé par les pairs
Résumé : The previously reported growth-promoting effect of insulin on explants of carcinogen-induced, hormone-dependent mammary carcinomas of the rat in organ culture has been studied in relation to carbohydrate metabolism. It was found that the growth-promoting effect of insulin, as measured by thymidine-14C incorporation into DNA, was accomplished with little or no effect on glucose consumption. Raising the concentration of glucose four- or eightfold above the usual level failed to increase cell proliferation. Substituting fructose, in a wide range of concentrations, for glucose failed to duplicate, even partly, the effect of insulin. At low concentration, in the presence of insulin, glucose became a rate-limiting factor. In this case, glucose consumption decreased to lower values than those observed in the absence of insulin; moreover, addition of pyruvate markedly raised the depressed level of cell proliferation. In contrast, in the absence of insulin, pyruvate always failed to stimulate cell proliferation. These data led to the conclusion that two main properties of insulin which are usually associated in tissue and organ culture, namely stimulation of glucose metabolism and promotion of growth, are dissociated in explants of the rat mammary carcinoma, possibly by virtue of selective dedifferentiation. In addition, these data strongly suggest that promotion of growth by insulin in these explants was not mediated through a stimulating effect on glucose uptake and utilization. © 1968.