IRS1 null mice have much reduced growth (30-60% of control) [39,64], whereas IRS2 null mice have almost normal growth (about 90% of control), but develop type 2 diabetes [65], therefore IRS1 is thought to be downstream of the IGF1 receptor, and IRS2 downstream of the insulin receptor (Table 3). Here, IRS2 is linked to type 2 diabetes mellitus.