Insulin elicits its divergent metabolic and mitogenic effects by binding to its specific receptor, which belongs to the family of receptor tyrosine kinases. The activated insulin receptor phosphorylates the intracellular substrate IRS-1, which then binds various signalling molecules that contain SRC homology 2 domains, thereby propagating the insulin signal. Among these IRS-1-binding proteins, the Grb2-Sos complex and the protein tyrosine phosphatase SHP-2 transmit mitogenic signals through the activation of Ras, and phosphoinositide 3-kinase is implicated in the major metabolic actions of insulin. Although substantial evidence indicates the importance of IRS-1 in insulin signal transduction, the generation of IRS-1-deficient mice has revealed the existence of redundant signalling pathways.