Recently, a novel experimental approach to mimic the pathophysiology of T2D model was proposed, based on the administration of the insulin receptor antagonist (IRA), the S961 peptide, which has been shown to induce transient hyperglycemia and hyperinsulinemia in mice [15] and rats [16], as well as to elicit NADPH-dependent endothelial nitric oxide synthase (eNOS) uncoupling in rabbits [17] and microvascular complications in mice [18]. Here, INSR is linked to Hyperglycemia.