Regulation of IGF-I and -II by insulin in primary cultures of fetal rat hepatocytes

During perinatal development, insulin and nutrients, rather than GH, regula te the IGF system. A selective primary culture of fetal rat hepatocytes has been established in our laboratory to elucidate the molecular mechanism of action of the above regulatory factors on IGF-I and -II gene expression du ring the late fetal period of the rat. In this model we have previously rep orted a regulatory role for glucose on IGF-I and -II synthesis and secretio n. In the same experimental model, we now report that doses of insulin (0.1 -5 muM) within the physiological range in rat fetuses during the last stage s of gestation evoke an increase of IGF-I and -II mRNA abundance. Insulin r egulated in a parallel manner IGF peptide secretion, and an excellent corre lation was observed between IGF-I and -II mRNA and IGF-I and -II peptide le vels in the conditioned media in response to the hormone. Finally, the insu lin-induced rise in IGF-I and -II mRNA was not mediated by stimulation of g ene transcription but by increased transcript stability. The results suppor t the hypothesis that insulin plays a major role in IGF regulation at immat ure stages of development.