I-European research, the cradle of the discovery of the antidiabetic hormone: the pioneer roles and the relevance of Oskar Minkowski and Eugène Gley

Abstract

Aims The introduction of hormonal treatment in severe diabetes in 1922 represented a clinical and social impact similar to that of antibiotic therapy. In October 1923, the Assembly of the Karolinska Institute decided to award the Nobel Prize in Physiology or Medicine to the Canadian Frederick Grant Banting and the Scottish John James Rickard Macleod, researchers at the University of Toronto (UT), for "the discovery of insulin a year before". A few weeks later, European and American researchers protested the decision. The controversy remains to this day. Methods We have conducted a comprehensive review of primary and critical sources focused on the organotherapy of animal and human diabetes mellitus since 1889, when Oskar Minkowski demonstrated the induction of experimental diabetes by total pancreatectomy in the dog, until the spring of 1923, when the Nobel Foundation had already received all the nominations for the award in Physiology or Medicine. Results The in-depth analysis of all these sources revealed that Europe was the cradle of the discovery of the antidiabetic hormone. The discovery involved multiple research steps headed by a long list of key investigators, mainly European. Conclusion Marcel Eugène Émile Gley was the first to demonstrate the presence of the “antidiabetic principle” in extracts from “sclerosed” pancreas. The French physiologist pioneered the successful reduction of glycosuria and diabetic symptoms by the parenteral administration of pancreatic extracts to depancreatized dogs in experiments developed between 1890 and 1905, antedating insulin in two decades.

100 Years since the Discovery of Insulin, from Its Discovery to the Insulins of the Future

“…In 1815, Michel-Eugene Chevreul identified glucose in urine; a few years later, in 1869, Paul Langerhans described nests of cells in the pancreas; these were later named the “Islets of Langerhans” by Gustave-Edouard Laguesse in 1983 ( Figure 1 ). Twenty years later, in 1889, Von Mering and Minkowsky, two physiologists from the University of Strasbourg, removed a pancreas to test it in a living organism (dog) and observed that its absence induced an excess of sugar in the urine, and subsequently, they found that the pancreas secreted something that reduced the levels of sugar [ 4 , 5 ]. A few years later, in 1891, Eugène Gley confirmed this discovery and revealed that the atrophy of the acinar pancreas did not result in experimental diabetes, and looked for pancreatic extracts which reduced glucosuria; however, Gley did not publish his results [ 5 ].…”

“…Twenty years later, in 1889, Von Mering and Minkowsky, two physiologists from the University of Strasbourg, removed a pancreas to test it in a living organism (dog) and observed that its absence induced an excess of sugar in the urine, and subsequently, they found that the pancreas secreted something that reduced the levels of sugar [ 4 , 5 ]. A few years later, in 1891, Eugène Gley confirmed this discovery and revealed that the atrophy of the acinar pancreas did not result in experimental diabetes, and looked for pancreatic extracts which reduced glucosuria; however, Gley did not publish his results [ 5 ]. Instead, it was Georg Ludwig Zuelzer who was the first to publish the use of pancreatic extracts, which he called “Acomatol”, on diabetic dogs.…”

The Current Status of Allogenic Islet Cell Transplantation

“…The origin of transplantation as a treatment for diabetes dates back to the 1800s (Figure 2), before islet cells had been isolated and properly understood. Oskar Minkowski is credited with the initial discovery of the pancreatic origin of diabetes after conducting total pancreatectomies in dogs in 1889 and noticing the development of glucosuria immediately postoperatively [5]. Two years later, Emmanuel Hedon furthered Minkowski's research by auto-transplanting pancreatic remnants subcutaneously into de-pancreatized dogs.…”

“…His experiments illustrated that if the transplanted remnant remained in place with an adequate vascular supply, the dog would survive. However, as soon as the graft was removed, there was a rapid onset of glycosuria and progression to death [5]. In 1893, Watson-Williams attempted the first pancreatic transplant in humans by transplanting pieces of sheep's pancreas subcutaneously into a 13-year-old patient with diabetic ketoacidosis [5].…”

“…However, as soon as the graft was removed, there was a rapid onset of glycosuria and progression to death [5]. In 1893, Watson-Williams attempted the first pancreatic transplant in humans by transplanting pieces of sheep's pancreas subcutaneously into a 13-year-old patient with diabetic ketoacidosis [5]. The xenograft experiment failed, and the patient died a few days later, triggering a turn away from focusing on the pancreatic role in diabetes.…”