Interestingly, it has been proposed that brain GLP-1-mediated peripheral glucoregulation is rendered dysfunctional due to chronic overstimulation in a diabetic state, and that chronic intracerebroventricular administration of Ex-9 can block the development of hyperinsulinemia and insulin resistance in mice fed with a high-fat diet [44,60,99]. This evidence concerns the gene GLP1R and Hyperinsulinemia.