Action sites of western medicine in diabetes treatment. Hypoglycemic medicines restore euglycemia via several types, including insulin secretagogues (sulfonylureas, meglitinides), insulin sensitizers (biguanides, metformin, thiazolidinediones), alpha-glucosidase inhibitors (miglitol, acarbose).

Action sites of herbs in diabetes treatment. The efficacy of hypoglycemia herbs has been mediated by increasing insulin secretion (ginseng, bitter melon, aloes, biophytum sensitivum), enhancing glucose uptake by adipose and muscle tissues (ginseng, bitter melon and cinnamon), inhibiting glucose absorption from intestine (myrcia and sanzhi) and inhibiting glucose production from heptocytes (berberine, fenurgreek leaves).

Insulin secretion and pancreatic-β-cell apoptosis. Glucose is taken up into β-cells via glucose transporters. It is metabolized in glycolysis and Krebs cycle, resulting in an increased ratio of ATP to ADP in the cytoplasm. This closes ATP-sensitive potassium channels (KATP channels), leading to cell membrane depolarization and subsequently opening voltage-gated Ca2+ channels. These changes increase free Ca2+ concentration ([Ca2+]i) in cytoplasm and eventually triggers insulin secretion. In apoptosis, stimuli promotes the release of caspase activators from mitochondria and result in the activation of caspases procedure, by cleaving the effector caspases, which interacts with a variety of cellular proteins, resulting in directly or indirectly the morphological and biochemical characteristics of cell apoptosis. The action sites of hypoglycemia herbs are indicated with a narrow.

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.