We investigated this possibility in vitro, to dissociate the various components of obesity and found that while transient/chronic hyperglycaemia or brief insulin exposure were ineffectual, prolonged high-dose insulin treatment to induce insulin resistance33 reduced free Raptor (Fig. 1f and Supplementary Fig. 1g). The gene discussed is RPTOR; the disease is obesity due to melanocortin 4 receptor deficiency.