It was previously shown that increased phosphorylation of insulin receptor substrate 2 (IRS2) serine in a hyperglycemic state decreased GRB2 bridging protein expression in diabetic neuropathy rats, whereas GRB2 expression was increased in diabetic retinopathy mice because it bound to phosphorylated insulin receptor substrate 1 (IRS1), activated the MAPK signaling pathway, and was also involved in vascular endothelial growth factor signaling to lead to retraction (25–27). This evidence concerns the gene IRS1 and diabetic retinopathy.