A hallmark of type 2 diabetes is the increased expression of IR/IGF-1R hybrids which are thought to restrict insulin signalling in favour of IGF-1,5 a scenario we,18,19 and others, have demonstrated may be present in the endothelium20 and vasculature.21 Understanding how hybrid receptors are regulated and activated in the vasculature is hence of importance to our understanding of obesity-related perturbation of insulin signalling and vascular dysfunction. The gene discussed is INSR; the disease is obesity due to melanocortin 4 receptor deficiency.