Our finding that insulin can directly activate Akt/mTOR signalling and induce expression of HIF-1α/VEGF in vivo retina endothelial cells, echoes our in vivo observation that long-term treatment of insulin may increase the risk of neovascularization in the retina of diabetic animals, and provide scientific evidence to support the claims of the unfavourable effect of insulin in diabetic retinopathy control. This evidence concerns the gene INS and diabetic retinopathy.