IRS1 and Insulin resistance: First, insulin resistance leads to the increase of serine phosphorylation of insulin receptor substrate 1 (p-IRS-1), a key insulin signal factor in myocardial cells, which in turn damages the signal transduction pathway of phosphatidylinositol 3-kinase (PI3K)- protein kinase B (also known as AKT), then blocks the shift of glucose transporter 4 (GLUT4) to the cell membrane and reduces the intake of glucose in the heart (47).