100 Years of insulin: Lifesaver, immune target, and potential remedy for prevention

Abstract

In this review, we bring our personal experiences to showcase insulin from its breakthrough discovery as a life-saving drug 100 years ago to its uncovering as the autoantigen and potential cause of type 1 diabetes and eventually as an opportunity to prevent autoimmune diabetes. The work covers the birth of insulin to treat patients, which is now 100 years ago; the development of human insulin, insulin analogs, devices, and the way into automated insulin delivery; the realization that insulin is the primary autoimmune target of type 1 diabetes in children; novel approaches of immunotherapy using insulin for immune tolerance induction; the possible limitations of insulin immunotherapy; and an outlook on how modern vaccines could remove the need for another 100 years of insulin therapy. INSULIN SAVES LIVESThe birthday of insulin Studying medicine in his home town of Berlin, Germany, Thomas Danne was always fascinated by the story of insulin. It started in Berlin in 1869, when a medical student, Paul Langerhans, described in his dissertation the pancreatic islet cells named after him. 1 In 1909, de Meyer gave the name ''insulin'' to the unknown substance formed in Langerhans' islets. 2 In 1921, two Canadians, Frederick Banting, a surgeon with a vision but no formal research training, and Charles Best, a medicine student, made it happen. 3 The birthday of insulin on January 11, 1922, was also the beginning of pediatric diabetology, when 14-year-old Leonard Thompson, diagnosed with diabetes in 1919, was treated at Toronto General Hospital with the extract prepared by Banting and Best. However, the researchers considered it a complete failure, since the glucose decreased only from 440 to 320 mg/dL, ketones remained present, and the local outcome was sterile abscess in the buttocks. 4 James Collip refined the extraction progress, and on January 23-24, 1922, his extract normalized the glucose and made the ketones disappear. On February 5, 1922, Banting and Best published the article ''The internal secretion of the pancreas.'' 5 Banting and his boss and head of the laboratory, J.R.R. Macleod, were rewarded with the Nobel

The countdown to type 1 diabetes: when, how and why does the clock start?

“…The clinical manifestation of type 1 diabetes is preceded by pre-symptomatic islet autoimmunity [ 1 , 2 ], which is diagnosed by the detection of islet autoantibodies [ 3 ]. The presence of more than one islet autoantibody (classified as stage 1 of type 1 diabetes disease) is associated with a high probability of developing clinical, symptomatic diabetes over the following years [ 4 ].…”