INS and Hyperinsulinemia: We found that both hyperinsulinemic (Figure 4A) and hyperglycemic (Figure 4B) lean Zucker rats had impaired D1 receptor-mediated vasorelaxation, accompanied by decreased D1 receptor expression (Figure 4C) and increased D1 receptor phosphorylation (Figure 4D), but the dysfunction of the D1 receptor was greater in the hyperinsulinemia than hyperglycemia model, indicating that insulin plays a more important role than hyperglycemia in the impairment of arterial D1 receptor-mediated relaxation (Figures 4A-D).