Wednesday, August 12, 2020

Extraction of insulin from islet of Langerhans

The term of “diabetes” was coined by the Greek Aretaeus in the second century AD. In 1776, the Liverpool physician, natural philosopher and experimental physiologist Matthew Dobson (1732 or 1735–1784) discovered that urine of diabetic patients is sweet because of excess in sugar.

In 1869, Paul Langerhans discovered with his doctoral thesis the existence of clusters of cells in the pancreas, despite their function was unknown. Islets of Langerhans are islands of endocrine cells scattered throughout the pancreas. However, the link between diabetes and the pancreas was not discovered until 1889 by Minkowski and von Mering.

In 1909, the Belgian Jean de Meyer coined the term “insuline” to refer to the “internal secretions” of the pancreas, from the Latin word for “island”. In 1910 and later in 1916, in London, Sir Edward Albert Sharpey-Schafer described in depth that the pancreatic islands are able to secrete a substance capable of controlling glucose metabolism.

There were many attempts to isolate the “internal secretions” of the pancreas during the first two decades of the twentieth century.

It was not until October 1920 that Fredrick G. Banting, a young orthopedic surgeon, got inspired while reading an article to prepare a lecture about the pancreatic islets of Langerhans and diabetes. He believed that earlier failures were attributable to the destructive action of trypsin.

Since November 1920, Banting began working in a laboratory led by John James Richard MacLeod. Banting's goal was to isolate the hormone secreted by the pancreatic islands.

He hypothesized that ligation of the pancreatic ducts before the extraction of the organ would destroy the acinar tissue, the enzyme-secreting compartment of the pancreas, while the islets of Langerhans would remain intact and able to produce the internal secretion regulating sugar metabolism.

In 1921 the Canadian scientists Banting, Charles H. Best, J. J. R. Macleod and James B. Collip discovered insulin, a peptide (small protein hormone) which lowers blood sugar. They extracted insulin from the islets of animal pancreases.

They closed the pancreatic ducts with a technique designed by Banting to get the degeneration of the pancreatic exocrine tissue and to obtain a pancreatic islet from the pure state. With this liquid extract, for the first time, in the history of medicine, Banting and Best found the way to control glucose in a diabetic animal.

Their experiments produced an extract of pancreas that reduced the hyperglycemia and glycosuria in dogs made diabetic by the removal of their pancreases. They next developed a procedure for extraction from the entire pancreas without the need for duct ligation.

The discovery of insulin, and the demonstration that it can lower blood glucose in dogs, by Frederick Banting and Charles Best in 1921, and its subsequent development for clinical use, in collaboration with John Macleod and James Collip, led to the award of the Nobel Prize in Physiology or Medicine to Banting and Macleod in 1923.
Extraction of insulin from islet of Langerhans
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