Insulin and IGF-1 induce different patterns of gene expression in mouse fibroblast NIH-3T3 cells: Identification by cDNA microarray analysis

The IGF-1 receptor and the related insulin receptor are similar in structur e and activate many of the same postreceptor signaling pathways, yet they m ediate distinct biological functions. It is still not understood how the sp ecificity of insulin vs. IGF-1 signaling is controlled. In this study, we h ave used cDNA microarrays to monitor the gene expression patterns that are regulated by insulin and IGF-1. Mouse fibroblast NIH-3T3 cells expressing e ither the wild-type human IGF receptor or the insulin receptor were stimula ted with either IGF-1 or insulin, respectively. Thirty genes, 27 of which w ere not previously known to be IGF-1 responsive, were up-regulated by IGF-1 but not by insulin. Nine genes, none of which was previously known to be i nsulin responsive, were up-regulated by insulin but not by IGF-1. The IGF- and insulin-induced regulation of 10 of these genes was confirmed by Northe rn blot analysis. Interestingly, more than half of the genes up-regulated b y IGF-1 are associated with mitogenesis and differentiation, whereas none o f the genes specifically up-regulated by insulin are associated with these processes. Our results indicate that under the conditions used in this stud y, IGF-1 is a more potent activator of the mitogenic pathway than insulin i n mouse fibroblast NIH-3T3 cells.