This is why the hyperinsulinemia that is typically associated with IR, in an attempt to maintain glucose levels in the normal range, ends up increasing the activity of the MAPK pathway, with prevalence of deleterious effects at the cardiovascular level due to mitogenic and proliferative actions, and to over exposure to ET-1, which, in the presence of reduced NO production, results in serious endothelial dysfunction [18]. This evidence concerns the gene EDN1 and hyperinsulinism.