JOURNEY OF INSULIN TILL INSULIN GLARGINE

Until the discovery of insulin in the 1920s, diabetes mellitus was primarily encountered and perceived as a fatal disease, usually occurring in younger individuals. With the classic work of Banting, Best, and others, however, came the prospect of life-saving insulin replacement therapy, which was quickly pressed into clinical service 1 . Since its discovery and first clinical use in the 1920s, insulin therapy has revolutionized the treatment and natural history of both type 1 and type 2 diabetes mellitus 2 . Historically, in 1890, von Mering and Minkowski1 identified the crucial link between the pancreas and diabetes as evidenced by the diabetic phenotype they induced in dogs after pancreatectomy. Physiologist Sharpey-Schafer hypothesized that pancreatic islets might produce an “internal secretion” or hormone involved in glucose homeostasis. Consequently, the first 2 decades of the twentieth century witnessed numerous attempts to isolate this internal secretion. Frederick G. Banting conceived of a novel method of isolating the internal secretion by deliberately inducing atrophy of the acinar cells of the exocrine pancreas via duct ligation in dogs, to diminish the potentially destructive effect of digestive enzymes on the islet hormone 3 . In the summer of 1921, assisted by Charles H. Best in the laboratory of John J.R. MacLeod at the University of Toronto, Banting became the first to demonstrate that pancreatic islet extracts consistently reduced hyperglycemia and glycosuria in depancreatized, diabetic dogs 4 . Later that year, with the expertise of biochemist James B. Collip, a novel protocol was developed to purify what they later named “insulin” (Latin: insula, island), from pancreatic islets of whole bovine pancreata without the need for pancreatic duct ligation experiments. The first successful therapeutic use of pancreas extracts of bovine insulin occurred at the Toronto General Hospital on January 11, 1922, on a 14-year-old patient, Leonard Thompson, who was admitted with type 1 diabetes 5 . Such products greatly reduced the incidence of early mortality from diabetic ketoacidosis and completely revolutionized diabetes therapy. In 1923, the Nobel Prize in Medicine and Physiology was jointly awarded to Banting and MacLeod for what is considered one of the greatest advancements in modern medicine 2 .

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