Insulin signal pathway and insulin insensitive. The inner part of IR reveals a tyrosine kinase activity and coupled with proteins of Src-homology-collagen-like protein (SHC) and multifunctional docking proteins IRS-1 and IRS-2. The interaction of insulin and IR activates its tyrosine activity and phosphorylates the coupled SHC and subsequently activates, in turn, a series of signal proteins, including the growth factor receptor-binding protein 2 (Grb2), and the ras small guanosine 5'-triphosphate-binding protein. The in turn signaling leads to an activation of the MAPK cascade involved in mitogenesis and the open status of a hexose transporter protein (GLUTs), which is located in the cell membrane and is the only pump to take into glucose for cells. The decreased serine/threonine phosphorylation of IR, inactivates hexokinase and glycogen synthase, as well as defects in the phosphorylation of glucose transporter protein (GLUT4) and genetic primary defect in mitochondrial fatty acid oxidation, leading to insulin resistance and an increase of triglyceride synthesis contribute to this insulin insensitivity. The action sites of hypoglycemia herbs are indicated with an arrow.