Insulin and Diabetes

The year 2021 marks the 100th anniversary of the discovery of insulin. This pancreatic extract lowered the high blood glucose levels in humans for the first time and enabled the lifesaving treatment of patients with diabetes. Before the discovery of insulin, since ancient times, a diagnosis of diabetes meant certain death.

In type 1 diabetes, the body’s autoimmune system attacks and destroys the beta cells that make the hormone called insulin, preventing the production of insulin in the body. Whereas, in type 2 diabetes the body doesn’t make enough or properly functioning insulin, known as insulin resistance. In both types, without the properly functioning insülin, the glucose in the blood accumulates. Without diabetes, the body’s cells use insulin to take the glucose from our blood into cells and uses this glucose for energy production.

Frederick Banting and Charles Best discovered insulin under the directorship of John Macleod at the University of Toronto, Canada, in 1921. With the help of James Collip, they purified insulin and made it available for the first successful treatment of diabetes patients. This discovery brought the Nobel prize in physiology or medicine in 1923 to Banting and Macleod “for the discovery of insulin”, causing controversy at the time of the awarding. Thus, Banting shared the honors and the prize money with Best, while Macleod shared his part with Collip. A former member of the Nobel committee later claimed to award John Macleod and not Charles Best and Nicolae Paulescu —who was the first to develop a pancreatic extract which normalized blood glucose in a dog with diabetes —, to be the worst error of the commission. Considering the record short time between the discovery and the prize and the circumstances of the post-war times (Nobel prizes for several years were not awarded due to war), the probable cause of this error was the rush of the committee to acknowledge this breakthrough achievement without a more detailed investigation.

As noted by Banting in his Nobel lecture, insulin is not a cure for diabetes; it is instead a treatment. Diabetes research has advanced considerably in understanding the pathogenesis of the different types in the past 100 years. Although there are significant advances in patient care, a cure has remained elusive. Indeed, scientists made seminal contributions to the understanding of the physiology of insulin’s action and secretion during the 100 years beginning with the discovery of insulin.

By the end of 1922, the drug company Eli Lilly was able to carry out the mass production of insulin. Also, a visit of the Danish zoophysiology professor and Nobel Laureate August Krogh to Banting’s Lab in Toronto has spread the know-how to produce insulin to Nordic countries. In 1923, nearly all insulin in the world was being produced by either Eli Lilly in the USA or Connaught Laboratories in Canada. By 1923 Krogh and his colleagues started producing insulin in Copenhagen, Denmark, at their Nordisk Insulin Laboratory. This laid the foundations of the drug company Novo Nordisk, which is currently one of the world’s leading drug companies in insulin production. By the mid-1930s, attempts were made to create a longer-acting form of insulin in the body. These longer-acting forms of insulin became widely available in the late 1940s. The next major milestone came with the British biochemist Frederick Sanger’s discovery of the sequence of insulin (the first protein ever sequenced), which brought him the Nobel Prize in Chemistry 1958. This paved the way for a shift from the production of animal-based insulin to synthetic human insulin.

With the development of recombinant DNA technology, multiple forms of insulin were clinically available by the 1980s. There was still research going on to supply the needs for longer-acting forms of insulin for between mealtimes in the 2000s. Immense research progress continues to this day, with many new insulin analogues with superior pharmacokinetic and pharmacodynamic properties are continuously entering clinical trials. Considering the currently ongoing research efforts all around the world, it is expected that possible cures are to come in the next one or two decades.

References

Fralick, M., & Zinman, B. (2021). The discovery of insulin in Toronto: beginning a 100 year journey of research and clinical achievement. Diabetologia, 1-7.

Perreault, L., Skyler, J. S., & Rosenstock, J. (2021). Novel therapies with precision mechanisms for type 2 diabetes mellitus. Nature Reviews Endocrinology17(6), 364-377.

Polyzos, S. A., & Mantzoros, C. S. (2021). Diabetes mellitus: 100 years since the discovery of insulin. Metabolism, 154737.

Rydén, L., & Lindsten, J. (2021). The history of the Nobel prize for the discovery of insulin. Diabetes Research and Clinical Practice175, 108819.

Nature milestones in diabetes. Nature Reviews Endocrinology, 17 June 2021, https://www.nature.com/immersive/d42859-021-00002-5/index.html.

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