46 IGF-1 receptor regulation of VEGF action is mediated at least in part through control of VEGF activation of p44/42 mitogen-activated protein kinase, establishing a hierarchical relationship between IGF-1 and VEGF receptors. Therefore, these findings establish an essential role for IGF-1 in angiogenesis and demonstrate a new target for control of retinopathy and also explain why diabetic retinopathy initially increases with the onset of insulin treatment. 47–49. This evidence concerns the gene WNK2 and diabetic retinopathy.