Insulin structure discovery and obtaining it BY Beata

Insulin – structure, discovery and obtaining it. BY Beata Berke

What is insulin? Insulin is a hormone central regulating carbohydrate and fat metabolism in the body. Insulin causes liver cells, muscle cells and fat tissue to take up glucose from the blood and store it as glycogen in the liver and muscle.

Production of insulin Insulin is producted by the pancreas, which has two important functions : 1. Producing hormones – insulin and glucagon which regulate blood sugar levels. 2. Producing pancreatic digestive enzymes. Insulin is released when any of the several stimuli are detected– stimuli include ingested protein and glucose in the blood from digested food.

Insulin against Alzheimer’s Insulin and its related proteins have been shown to be produced inside the brain, and reduced levels of these proteins are linked to Alzheimer’s disease.

Insulin structure Insulin is a peptide hormone composed of 51 amino acids and has a molecular weight of 5808 Da.

Insulin is produced and stored in the body as a hexamer , while the active form is the monomer.

Hexamer is more stable then the monomer, which is better for practical reasons. Monomer is a much faster-reacting drug, it means that insulin injections do not have to precede mealtimes by hours.

Insulin is produced by beta cells in the islets of Langerhans, which release insuln in two phases: The first phase release is triggered in response to rising or increased blood glucose levels. The second phase is a sustained, slow release of newly formed vesicles triggered independently of sugar. Beta cells in the islets of Langerhans take up as much as 60%-80% of all the cells.

Insulin mutations Mutations in the insulin gene can cause type I or type II diabetes. Reserchears have found at least 10 mutations - they suspect that the mutations alter the way insulin folds during its synthesis. Reserchears suggest that these improperly folded proteins interfere with other cellular processes in ways that eventually kill the cells that produce insulin.

Most strongly influenced by insulin are the muscle cells and fat cells. These cells are important because of their central role in movement, breathing and circulation. Together these cells account about twothirds of all cells. Avarage life of insulin is 3 -6 min.

Actions of insulin on the human metabolism Control of the cellural intake of certain substances. Increase of DNA replication and protein sythesis. Modification of the activity of numerous enzymes.

Insulin for medical purposes Insulin is being produced biosynthetically using recombinant DNA technology. More recently, reserchers have succeded in introducing the human insulin gene into plants and in producing insulin in them. This technique is set to reduce production costs. Before it was possible to produce insulin biosynthetically it wa aquired from animals and purified so it could be used as injections.

Although insulin which is aquired biosynthetically is a precise copy of the human insulin gene, they have been designed to have an effect much faster.

History of insulin

Paul Langerhans was a medical student in Berlin in 1869. He was studying the structure of pancreas under the microscope when he noticed tissue clumps scatarred throughout the pancreas. He named them as the islets of Langerhans.

Oscar Minkowski In 1889, Polish-German physician Oscar Minkowski in collaboration with Joseph von Mering, removed the pancreas from a healthy dog to test its assumed role in digestion. On testing the urine , they found sugar in the dog’s urine, establishing for the first time a relationship between the pancreas and diabetes.

In 1916, a Romanian professor of physiology Nicolae Paulescu, was the first to isolate insulin. In 1921. Nicolae published four papers explaining his research. 8 months later his work was confirmed by doctor Frederick Grant Banting and biochemist J. J. R. Macleod, who were later awarded the Nobel prize.

Nicolae Paulescu was the dicoverer of insulin, however because of his anti-semitic views he has been ereased from the history of medicine as the discoverer of isnulin.

In 1920, Canadian Frederick Banting was reading one of Mikowski’s papers and concluded that it was the digestive secretions that Minkowski had originally studied that were breaking down the islet secretions, thereby making it impossible to extract successfully. The idea was the pancrea’s internal secretions, which, it was supposed, regulates sugar in the bloodstream, might hold the key to the treatment of diabetes. A surgeon by training, Banting knew certain arteries could be tied off that would lead to atrophy of most the pancreas, while leaving the islets of Langerhans intact.

In 1921, Banting travaled to Toronto to explain his idea to J. J. R. Macleod, who was Professor of Physiology at the University of Toronto. He asked Macleod if he could use his lab to test his idea. Eventually he agreed to let Banting use his lab and supplied him with ten dogs on which to experiment and a lab assistant Charles Best.

John James Rickard Maclod When the Professor returned from his summer vacation to the University of Toronto and saw the progress Banting and Best had made, he decided to let Banting contionue his research, supplied him with more dogs, bigger lab and pointed out the flaws in his research.

Frederick Banting After Bantings discovery, the Canadian goverment funded Bantings , so he could continue his research. King George V crowned Banting Ser.

Chales Best Macleod supplied Banting with two lab assistants – Charles Best and Clark Noble. Since Banting required only one lab asisstant, Best and Noble flipped a coin to see which would assist Banting for the first half of the summer. Best won, and took the first shift as Banting’s asisstant. Unfortunate for Noble Banting decided to keep Best for the entire summer.

The first insulin injection was made on January 11, 1922, Leonard Thomson, a 14 -year-old diabetic who lay dying at the Toronto General Hospital. However, the extract was so impure Thompson suffered a severe allergic reaction, and further injections were canceled. Over the next 12 days, Collip developed a second dose – purified exctract, which Banting injected Thompson on January 21. The second injection was succesful, with no side-effects and also in completely eliminating the glycosuria sign of diabetes.

James Collip James helped Banting to purify the insulin exctract, but Banting, Best and Collip didin’t work well together so after a year Collip left the group.

In 1922, Best managed to improve his techniques to the point where large quantities of insul could be exctracted on demand, but the preparation remained impure. The drug firm “Eli Lily and Company” united with Basting and in November, “Eli Lily and Company” made a major breakthrough and were able to produce large quantities of highly refined insulin. Insulin was offered for sale shortly after.

Herbert Boyer was the scientist first who succeded in making a synthetic “human” insulin through gene-engeneering in a laboratory in 1977.

“Eli Lily and Company” partnered up with “Genetech” the company founded by Boyer, went on in 1982 to sell the first commercionally available biosynthetic human insulin under the brand name “Humilin”. The patent for insulin was sold to the University of Toronto for one half-dollar.

Nobel prizes In 1923 the Nobel prize committee awarded Frederick Banting and J. J. R. Macleod. They were awarded the Nobel Prize in Physiology for the discovery of insulin. Banting, isulted that Best was not metioned, shared his prize with him and Macleod immediately shared his with James Collip.

Frederick Banting and his lab partner Charles Best

Dorothy Crowfoot Hodgkin In 1969, Dorothy determined the spatial conformation of the molecule, the socalled tertiary structure. She had been awarded a Nobel Prize in Chemistry in 1964 for the development of crystallography.

Frederick Sanger In 1958 british molecular biologist Frederick Sanger determined the primary structure of insulin. It was the first protein to have its sequence be determined. He was awarded the Nobel Prize in Chemistry for his work.

Rosalyn Sussman Yalow 1977 Rosalyn received the Nobel Prize in Medicine for the develpoment of radioimmunoassay for insulin.

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