The activation of the MR in diabetes may result from a combination of various mechanisms: increased ligand levels, either aldosterone for which increased synthesis has been reported from the adrenal upon obesity [48] or from local production for example by adipocytes [49], while increased MR activation by glucocorticoid may also occur, especially in cells where HSD2 is not expressed, together with the induction of local HSD1 activity associated to diabetes [50]. The gene discussed is NR3C2; the disease is obesity due to melanocortin 4 receptor deficiency.