Mitogenic actions of insulin on fetal and neonatal rat cells in vitro

Insulin has been implicated in the regulation of fetal growth. The aim of these studies was to determine if insulin has a direct mitogenic effect on fetal and neonatal rat cells in vitro. Myoblasts and fibroblasts were isolated from skeletal muscle and grown until myotube formation began or until fibroblasts were confluent. The cultures were then incubated in the presence of insulin (10(-5)-10(-1) units/ml) and its effects were measured by the cellular incorporation of [3H]-thymidine. Myoblasts from fetuses of 21 days of gestation showed a marked, linear dose-response to insulin, significant increases over control values being observed at 2 X 10(-5) units/ml or 2 X 10(-4) units/ml in five out of seven experiments. Neither myoblasts from 19-day fetuses or neonates nor fibroblasts from animals of any of the three ages showed a significant thymidine uptake response to insulin. Myoblasts released immunoreactive somatomedin-C-like activity into the culture medium, but this was not related to fetal age nor to the presence of insulin in the culture medium. The results suggest that insulin may have a direct role in fetal muscle growth.