The discovery that the PI3K/Akt/FOXO1 signalling axis regulates PlGF expression in endothelium is likely to be important for its pathological activity in diabetic retinopathy, atherosclerosis, and have wider implications in obesity and the metabolic syndrome, which are all characterised by endothelial dysfunction. This evidence concerns the gene PGF and obesity due to melanocortin 4 receptor deficiency.