Insulin alters cell proliferation during the early development of rodent kidney.

The effects of insulin on early differentiated 15-day fetal mouse kidneys were assessed using an organotypic culture system. High concentrations (30 to 125 mU/ml) of the hormone drastically reduced (50%) the incorporation of 3H-thymidine in replicating cells without affecting either differentiation of forming nephrons or epithelio-mesenchymal relationships. When compared to insulin-like growth factor-I or the potent phorbol ester PMA, the action of insulin seemed to specifically deregulate some components of the transductional machinery controlling cell proliferation. This is opposed to the previous demonstration of a positive influence of insulin on cell proliferation in the human fetal kidney. The results suggest that the common definition of insulin as a fetal growth promoter may depend on the developmental stage of each organ, particularly for the mammalian kidney.