INSR and Hyperinsulinemia: Firstly, hyperinsulinemia itself may downregulate insulin receptor by reducing the number and expression of insulin receptor in vascular endothelial cells, resulting in insulin resistance [8]; secondly, hyperinsulinemia activates protein kinase C (PKC) and abnormally increases its activity; thirdly, hyperinsulinemia promotes the proliferation of vascular smooth muscle cells and the synthesis and secretion of endothelin-1 (ET-1) in endothelial cells [9].