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Posted by on Feb 20, 2017 in Tell Me Why Numerous Questions and Answers |

Who Developed Insulin?

Who Developed Insulin?

Insulin extracts, which save the lives of many thousands of people, were developed by the combined efforts of three physiologists, Sir Frederick Banting from Ontario, Canada, Charles H. Best from Maine, United States, and John James Rickard Macleod from Perth, Scotland. In 1921 they became the first to obtain the hormone in a form consistently effective in the treatment of diabetes.

Normally, insulin is manufactured in the human pancreas, which lies behind the stomach. It enables the liver to store surplus sugar and the brain and muscles to be nourished by this essential food. When the insulin supply fails, the body can no longer use this fuel and an excess of sugar may spill through the kidneys into the urine. Diabetes, as this condition is called, previously meant almost certain death. The achievements of Banting, Best and Macleod at the University of Toronto, Canada, gave sufferers the prospect of a long and healthy life.

The three men were following up the work of two German physicians, Joseph Von Mering (1849-1908) and Oskar Minkowski (1858-1931), who in 1889 showed that the removal of the pancreas in dogs caused diabetes. With this link established, scientists set out to discover what contribution the pancreas made in preventing the disease.

In 1909 one of them Jean De Meyer (1878-1934) who was a Belgian clinician and physiologist, suggested the name insulin for this supposed internal secretion. Finally the three Toronto researchers discovered how to obtain the insulin from the pancreas of an Ox and inject it into human beings. In January, 1922, Banting administered crude insulin to a patient for the first time.

Banting and Macleod won the Nobel Prize for medicine in 1923, and Banting insisted on sharing his award with Best. Banting, who was knighted in 1934, was killed in a plane crash on February 21, 1941, while on a war mission connected with aviation medicine. Best succeeded him as head of the Banting and Best Department of Medical Research at Toronto University. Since their discovery, the extract has been refined, and many patients control their diabetes by administering their own insulin injections.

Insulin is a peptide hormone produced by beta cells of the pancreatic islets. It regulates the metabolism of carbohydrates, fats and protein by promoting the absorption of, especially, glucose from the blood into fat, liver and skeletal muscle cells. In these tissues the absorbed glucose is converted into either glycogen via glycogenesis or fats (triglycerides) via lipogenesis, or, in the case of the liver, into both.

Glucose production (and excretion into the blood) by the liver is strongly inhibited by high concentrations of insulin in the blood. Circulating insulin also affects the synthesis of proteins in a wide variety of tissues. It is therefore an anabolic hormone, promoting the conversion of small molecules in the blood into large molecules inside the cells. Low insulin levels in the blood have the opposite effect by promoting widespread catabolism.

Pancreatic beta cells (β cells) are known to be sensitive to glucose concentrations in the blood. When glucose concentrations in the blood are high, the pancreatic β cells secrete insulin into the blood; when glucose levels are low, secretion of insulin is inhibited.

Their neighboring alpha cells, by taking their cues from the beta cells, secrete glucagon into the blood in the opposite manner: increased secretion when blood glucose is low, and decreased secretion when glucose concentrations are high. Glucagon, through stimulating the liver to release glucose by glycogenolysis and gluconeogenesis, has the opposite effect of insulin.

The secretion of insulin and glucagon into the blood in response to the blood glucose concentration is the primary mechanism responsible for keeping the glucose levels in the extracellular fluids within very narrow limits at rest, after meals, and during exercise and starvation.

If pancreatic beta cells are destroyed by an autoimmune reaction, insulin can no longer be synthesized or be secreted into the blood. This results in type 1 diabetes mellitus, which is characterized by abnormally high blood glucose concentrations, and generalized body wasting.

In type 2 diabetes mellitus the destruction of beta cells is less pronounced than in type 1 diabetes, and is not due to an autoimmune process. Instead there is an accumulation of amyloid in the pancreatic islets, which disrupts their anatomy and physiology. Type 2 diabetes is characterized by high rates of glucagon secretion into the blood which are unaffected by, and unresponsive to the concentration of glucose in the blood glucose.

Insulin is still secreted into the blood in response to the blood glucose. As a result, the insulin levels, even when the blood sugar level is normal, are much higher than they are in healthy persons. There are a variety of treatment regimens, none of which is entirely satisfactory. When the pancreas’s capacity to secrete insulin can no longer keep the blood sugar level within normal bounds, insulin injections are given.

The human insulin protein is composed of 51 amino acids, and has a molecular mass of 5808 Da. It is a dimer of an A-chain and a B-chain, which are linked together by disulfide bonds. Insulin’s structure varies slightly between species of animals. Insulin from animal sources differs somewhat in effectiveness (in carbohydrate metabolism effects) from human insulin because of these variations. Porcine insulin is especially close to the human version, and was widely used to treat type 1 diabetics before human insulin could be produced in large quantities by recombinant DNA technologies.

The crystal structure of insulin in the solid state was determined by Dorothy Hodgkin. It is on the WHO Model List of Essential Medicines, the most important medications needed in a basic health system.

Content for this question contributed by Nicole Richardson, resident of Tampa, Hillsborough County, Florida, USA