These results collectively suggested that the transcription of Igf1r and Irs2 is regulated by the PI3K/FOXO1 signaling cascade, rather than the ERK cascade, and hyperinsulinemia promotes IGF1 resistance, at least partially, through the downregulation of Igf1r and Irs2 mRNA levels. Here, FOXO1 is linked to Hyperinsulinemia.