Basic introduction Chinese name: bovine insulin mbth: molecular weight of insulin from bovine insulin: 5733.53(Da) Property: protein hormone determination time: 1955 Function: blood sugar regulation, introduction, chemical structure, synthetic bovine insulin, scientific research, research process, scientific significance, medical function, anti-inflammatory, anti-arteriosclerosis and anti-platelet aggregation of bovine insulin. Treatment of mental illness, mechanism of action, regulation of glucose metabolism, regulation of fat metabolism, regulation of protein metabolism, and other functions Brief introduction of bovine insulin hybri-max； from bovine pancreas; Bovine insulin; Insulin (bovine insulin) number:11070-73-8 einecsno. : 234-29 1-2 Molecular formula: C254H377N65O75S6 Molecular weight: 5733.53 Bovine insulin is a regulatory sugar secreted by islet β cells in bovine pancreas. Its primary structure 1955 was determined by S.Sanger of Britain. Bovine insulin has anti-inflammatory, anti-arteriosclerosis, anti-platelet aggregation, treatment of hyperosteogeny, treatment of mental illness and so on. China is the first country to synthesize artificial bovine insulin. From 65438 to 0965, under the leadership of its director Wang Yinglai, Shanghai Institute of Biochemistry of Chinese Academy of Sciences cooperated with scientists from Peking University and Shanghai Institute of Organic Chemistry of Chinese Academy of Sciences. After many failures, crystalline bovine insulin, a bioactive protein, was finally synthesized artificially for the first time in the world. The synthesis of artificial bovine insulin marks an important step in the journey of understanding life and exploring the mystery of life. On September 1965, the total synthesis of crystalline bovine insulin was completed in China. After strict identification, its structure, biological activity, physical and chemical properties and crystal morphology are completely the same as those of natural bovine insulin. This is the first man-made protein in the world, and it is a gratifying step for human beings to understand life and uncover the mystery of life. This achievement won the first prize of China Natural Science in 1982. 1953, Englishman F. Sanger Sanger won the 1958 Nobel Prize in Chemistry for determining the primary structure of bovine insulin. Bovine insulin, abbreviated as BHb, can be characterized by small angle X-ray scattering. Chemical Structure Bovine Insulin is a protein molecule. Its chemical structure was determined and clarified by the British scientist Sanger in 1955: bovine insulin molecule is a double-stranded molecule, consisting of an A chain consisting of 2/kloc-0 amino acids and another B chain consisting of 30 amino acids, which is connected by two pairs of disulfide bonds, and the A chain itself has a pair of disulfide bonds. After the structural model of bovine insulin, scientists successively determined insulin from different biological sources and found that the chemical structure of bovine insulin was basically the same as that first determined by Sanger. The same is true of human insulin, except that threonine is used instead of alanine at the 8 th position of A chain, and isoleucine is used instead of valine at the 10 position; The 30th position of B chain was replaced by threonine. Synthesis of bovine insulin When V. Du Vigneand (1901-kloc-0/974) of the United States synthesized the first natural polypeptide hormone in 1953 (for which he won the Nobel Prize in Chemistry in 1955), Sanger (F F. completed all the sequencing work of insulin after 19 18- (for this reason, according to media reports, there were 10 research groups in the world during 1955- 1965. The determination of the research route is 1956, that is, in the second year after Sankin took the lead in determining the chemical structure of bovine insulin and won the Nobel Prize for it, another famous British scientist predicted in the internationally authoritative review article Nature that "synthetic insulin will be in the distant future". In this case, in the first half of 1958, the scientific and technical personnel of Shanghai Institute of Biochemistry, Chinese Academy of Sciences put forward to study "synthetic insulin", a significant and difficult basic scientific research project, and no one in the world has started to study it. However, for the synthesis of a kind of protein, it is necessary to obtain a pure product with the same biological activity and structure as the natural product in order to realize its total synthesis. Because the chemical structure of insulin molecule is complex, it also has the specific conformation of protein molecule. Therefore, the synthesis of insulin should not only complete the synthesis of peptide chains, but also fold the synthesized peptide chains into active molecules with the same conformation as natural insulin. In the insulin "family" at that time, only the chemical structure of bovine insulin had been determined, so the artificial synthesis of bovine insulin was carefully chosen. Once this major basic scientific research project was put forward, it immediately attracted the attention of our national leaders. With the consent and support of Director Wang Yinglai, it was decided to combine the existing protein Synthesis Group led by Niu Jingyi, protein Structure and Function Group led by Cao and the enzyme group led by Cao, and set up a "five-person leading group" headed by Cao, adopting a five-way scheme, namely 1, to master the key to disassembly and assembly of natural insulin A and B chains; 2. Strengthen the power of polypeptide synthesis and develop polypeptide synthesis; 3. Production of tissue raw materials, amino acids and peptide synthesis reagents; 4. Studying the conformation of insulin, separating and purifying natural peptides from the enzymolysis products of insulin as raw materials for chemical synthesis or enzymatic synthesis of larger peptides; 5. Carry out the research on enzymatic synthesis of peptide chain and peptide transfer reaction, and move towards the success of artificial synthesis of bovine insulin. The scientific research process actively organizes personnel according to this plan, so that all research work can be carried out quickly and smoothly. Firstly, under the guidance of Shen, the production process of amino acids was established, and several small fragments in insulin B chain were synthesized artificially. Later, Du Yucang, Zhang and others found that after S- sulfonation, natural insulin A and B chains can not only be separated and purified to obtain stable products, but also be easily recombined to obtain 5 ~ 10% insulin active products. The success of 1959 laid the foundation for the chemical synthesis of A chain and B chain in insulin synthesis. So far, the research on insulin synthesis has made initial progress. In the following years, although he devoted himself to "big corps operations", he did not make a substantive breakthrough. Until 1963, the yield of insulin produced by recombination of natural insulin A and B chains led by Zou Chenglu increased from 5 ~ 10% to about 50%. From 65438 to 0964, the peptide synthesis group led by Niu Jingyi and Gong Yueting synthesized B chain artificially. Recombinant insulin with natural A chain is successful. 1965 The Institute of Organic Science of China Academy of Sciences cooperated with the Department of Chemistry of Peking University, and the joint research team led by Wang You and Xing completed the chemical synthesis of insulin A chain. The B-chain of insulin synthesized by Shanghai Institute of Biochemistry was successfully recombined, and the synthetic bovine insulin crystal with the same specific activity and antigenicity as natural insulin was obtained by purification, and its crystal morphology and enzyme digestion map were also the same as natural insulin. The success of insulin synthesis declared that China scientists won the "World Champion" in this scientific competition after 8 years of research. Subsequently, Cao presided over the drafting of the paper, and this important scientific research achievement was first published in China Science in the form of a briefing in 1965 1 1 month, and the full text was published in 1966. Scientific Significance The synthesis of bovine insulin is a great leap in science, which marks the beginning of the era of synthesizing protein. It is a new important milestone in the development history of life science and a gratifying step in the great process of revealing the mystery of life. At the same time, it is also a great achievement in the basic research of natural science in China. Medical Function Anti-inflammatory Effect Diabetes and atherosclerosis are both inflammatory diseases. Severe patients, such as acute myocardial infarction, cerebral hemorrhage, sepsis, burns, etc. Even without diabetes, there will be stress hyperglycemia. 18 1 the death rate of critically ill patients abroad decreased by 43% after intravenous injection of insulin. After one week, C-reactive protein, inflammatory factors and nitric oxide decreased significantly. This shows that insulin can protect vascular endothelium, reduce lipid infiltration, inhibit inflammation of vascular wall and prevent organ failure. Anti-arteriosclerosis effect Apolipoprotein E gene defect is the cause of arteriosclerosis. Therefore, bovine insulin can be used in clinic without worrying that insulin will aggravate atherosclerosis. Some people have conducted experiments on oral insulin to treat atherosclerosis. Results The number of hardened blocks decreased and the hardened area decreased by 22%-37%. Because oral insulin has been destroyed by gastric juice and lost its hypoglycemic effect, anti-atherosclerosis is related to the anti-inflammatory and endothelial cell protection of insulin, but has nothing to do with hypoglycemic effect. Vascular endothelial cells with normal anti-platelet aggregation function have anti-platelet aggregation function and generally do not have atherosclerosis. Hyperglycemia, hyperlipidemia and hypertension will activate the oxidative stress reaction of endothelial cells, damage the endothelium, and platelet aggregation will play a role in fueling the situation. The hypoglycemic effect of bovine insulin indirectly protects endothelial cells. Treatment of hyperosteogeny bovine insulin can enhance the activity of osteoblasts, synthesize collagen fibers and promote the absorption of amino acids by bones. Bovine insulin can also promote the synthesis and absorption of vitamin D, which is beneficial to bone formation, and is most suitable for the treatment of diabetes complicated with osteoporosis. The treatment of bovine insulin hypoglycemia is mainly used for mental disorders and delirium tremens caused by toxic psychosis, and is also effective for anxiety, tension and neurasthenia. Different types of bovine insulin also have different effects. There are three types of (bovine) insulin, namely, medium-acting and long-acting bovine insulin, short-acting bovine insulin and ultra-short-acting bovine insulin which specifically reduces postprandial blood sugar. Medium and long-acting bovine insulin, also known as premixed insulin, is composed of short-acting insulin and medium-acting insulin in different proportions. The onset time is 1 ~ 2 hours, and the duration is about 12 hours. Inject twice a day, suitable for general patients with type 2 diabetes, but you can't eat for half an hour after injection. Short-acting bovine insulin is suitable for people with poor blood sugar control, especially those with high blood sugar after meals. They need to supplement another medium-and long-acting insulin before going to bed to maintain the basic insulin demand at night and keep the blood sugar stable at night. It takes effect 20 ~ 30 minutes after injection, lasts 4 ~ 6 hours, and needs to be injected 3 ~ 4 times a day. It is characterized by rapid onset, high concentration and strong hypoglycemic effect in unit time, and can be injected subcutaneously, intramuscularly or intravenously. Medical literature on insulin bovine insulin, which specifically reduces postprandial blood sugar, takes effect very quickly, and it begins to take effect after 10 minutes. Specially for patients with high postprandial blood sugar, they can eat after injection. Its duration is also shorter than other insulin, which is 1 ~ 2 hours. Mechanism of action Why does bovine insulin have such a great effect on patients? This must be discussed from the mechanism of bovine insulin. Insulin can regulate glucose metabolism, promote the uptake and utilization of glucose by whole body tissues, and inhibit the decomposition and heterogeneity of glycogen. Therefore, bovine insulin has the effect of lowering blood sugar. When insulin secretion is excessive, blood sugar drops rapidly, and brain tissue is most affected, which can lead to convulsion, coma and even insulin shock. On the contrary, insufficient insulin secretion or insulin receptor deficiency often leads to increased blood sugar; If the renal sugar threshold is exceeded, sugar will be excreted from urine, causing glycosuria; At the same time, due to the change of blood composition (containing excessive glucose), it will also lead to hypertension, coronary heart disease and retinal vascular diseases. The relationship between insulin and diabetes is the result of many functions: (1) It promotes the target cell membrane carrier in muscle and adipose tissue to transport glucose in blood into cells for metabolism. (2) Through the valence modification of * * *, phosphodiesterase activity is enhanced, cAMP level is decreased and cGMP concentration is increased, so that glycogen synthase activity is enhanced, phosphorylase activity is decreased, glycogen synthesis is accelerated and glycogen decomposition is inhibited. (3) Activate pyruvate dehydrogenase by activating pyruvate dehydrogenase phosphatase to accelerate the oxidation of pyruvate to acetyl coenzyme A and accelerate the aerobic oxidation of sugar. (4) inhibit gluconeogenesis by inhibiting the synthesis of PEP carboxykinase and reducing the raw materials of gluconeogenesis. (5) Inhibit hormone-sensitive lipase in adipose tissue, slow down fat mobilization, and increase the utilization of glucose in tissues. Regulating Fat Metabolism About Insulin Medical Literature Bovine insulin can promote the synthesis and storage of fat, reduce free fatty acids in blood, and inhibit the decomposition and oxidation of fat. Insulin deficiency can cause disorder of fat metabolism, decrease of fat storage, enhanced decomposition and increase of blood lipid, which can cause arteriosclerosis for a long time, and then lead to serious cardiovascular and cerebrovascular diseases; At the same time, due to the strengthening of fat decomposition, a large number of ketone bodies are produced, leading to ketoacidosis. It can regulate insulin metabolism in protein, promote the absorption of amino acids by cells and the synthesis of protein, and inhibit the decomposition of protein, which is beneficial to growth. The effect of pituitary growth hormone on protein synthesis can only be shown in the presence of insulin. Therefore, insulin is also one of the indispensable hormones for growth. Other functions of bovine insulin can promote potassium and magnesium ions to cross the cell membrane and enter cells; Can promote deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and adenosine triphosphate.