Table 1.
Main events and steps in the history of the discovery of insulin.
| Year | Major event |
|---|---|
| 1552 BC | One of the earliest, if not the earliest, descriptions of diabetes |
| 1675 | Thomas Willis coins the expression “diabetes mellitus” |
| 1682–1709 | Johann Conrad Brunner observes polydipsia and polyuria in dogs after partial pancreatectomy |
| 1706 | John Rollo, Surgeon-General to the Royal Artillery, treats a patient by dietary restriction |
| 1776 | Matthew Dobson discovers that urine of diabetic patients is sweet because of excess in sugar |
| 1788 | Thomas Crawley reports some clinical cases and links diabetes with pancreatic dysfunctions |
| 1850s | French physician Pierre Adolphe Piorry introduces hypercaloric dietary treatment |
| 1857 | French Claude Bernard links diabetes with excess glucose production |
| 1860s | Claude Bernard reports extensive physiopathological mechanisms of diabetes |
| 1865 | Introduction of the concept of “opotherapy” by Ancelet |
| 1869 | Paul Langerhans discovers cellular islets within the pancreas Noyes reports a case of retinitis in diabetic patients |
| 1870s | Bouchardat postulates a link between pancreas and diabetes |
| 1874 | Kussmaul describes the air hunger of ketoacidosis in diabetic patients |
| 1875 | Heidenhain demonstrates that extracts of the fresh pancreas possess no proteolytic capacities Nikolaus Friedreich postulates an indirect link between diabetes and pancreatic disorders mediated by sympathtetic nerve ganglia, in primis celiac ganglion and celiac plexus |
| 1876 | Étienne Lancereaux describes in depth the clinical differences between diabetes type 1 and type 2 |
| 1889–1893 | German physiologist Oskar Minkowski and physician Joseph von Mering, show that if the pancreas is removed from a dog, the animal gets diabetes |
| 1892 | Battistini and Capparelli try to cure diabetes by injecting pancreatic powder extracts |
| 1893 | Laguesse terms the pancreatic cellular islets after Langerhans (“islets of Langerhans”) On December 20, 1893, Dr. P. Watson Williams in Bristol, England, performs the first intervention of pancreas transplant |
| 1898 | Joslin proposes opium as treatment of diabetes |
| 1901 | Eugene L Opie correlates the hyaline degeneration of the islets of Langerhans with the occurrence of diabetes |
| 1906 | Wilhelm Heiberg develops a method for counting the islets of Langerhans and shows that they are low in diabetic patients |
| 1907 | J Rennie and T Fraser, from Aberdeen Royal Infirmary, experiment the effect of extracts of pancreatic islets from various teleostei, in particular the Lophius piscatorious, to a sample of 5 diabetic patients |
| 1908 | Zuelzer experiments pancreatic extracts termed Acomatol Zuelzer submits an application to the USA office of patents |
| 1909 | Forschbach publishes his findings of experiments with the Zuelzer's pancreatic extracts |
| 1909–1910 | Introduction of the name “insulin” by Belgian Jean de Meyer |
| 1910 | Joseph Pratt published “The relation of the pancreas to diabetes” in JAMA |
| 1912 | Zuelzer takes out an American patent entitled “Pancreas Preparation Suitable for the Treatment of Diabetes” (serial number 431,226) |
| 1913 | Murlin and Kramer propose that an optimal treatment of diabetic patients should lead to the restoration of respiratory quotient |
| 1914 | Rose experiments an alkaline pancreatic extract |
| 1915–1919 | Meltzer and Kleiner experiment the effect of a pancreatic solution highly diluted in NaCl |
| 1916 | Introduction of the name “insuline” by Sir Edward A Sharpey-Shafer of Edinburgh |
| 1918 | Hagedorn and the pharmacist Bierger Norman Jensen publish a micro-method for the determination of blood glucose |
| 1920 | Moses Barron publishes his “The relation of the islets of Langerhans to diabetes, with special reference to cases of pancreatic lithiasis” |
| 1921 | Dr Frederick Banting and medical student Charles Best perform experiments on the pancreases of dogs in Toronto, Canada Nicolae Paulescu presents his findings at the Rumanian Biological Association and later publish them in the “Reports of the French Society of Biology” and in the “Archives Internationales de Physiologie” Paulesco terms the impaired hormone in diabetic patients as pancreatin |
| 1922 | Bovin insulin was first given injected to humans Banting and Best publish their article entitled “The Internal Secretion of the Pancreas” in the “Journal of Laboratory and Clinical Medicine” |
| 1923 | Commercialization of Iletin Banting and Macleod are awarded the Nobel Prize in Physiology or Medicine August Krogh brought insulin to Scandinavia Petrén publishes his “Diabetes-studier” |
| 1924 | First attempt to graft pancreatic tissue to cure diabetes by the English surgeon Frederick Charles Pybus |
| 1925 | One of the earliest, if not the earliest, mentions of the possibility of administering insulin by breathing an aerosol |
| 1926 | JJ Abel obtains the first crystallization of insulin |
| 1936 | Sir Harold Percival (Harry) Himsworth introduces the concept of insulin resistance Protamine was utilized to produce a slow-release insulin: Hans Christian Hagedorn introduced protamine insulin in Denmark |
| 1949 | Production of the first standardized insulin syringes |
| 1951 | Development of amorphous lente insulins (IZS) |
| 1955 | Sanger characterized the amino acid sequence of human insulin |
| 1957 | Introduction of the technique of immunoassay by Solomon Berson and Rosalind Yalow |
| 1959 | Sanger is awarded the Nobel Prize in Chemistry |
| 1960 | First prototype of ambulatory insulin pump by Dr. Arnold Kadish |
| 1963 | Introduction of insulin pumps |
| 1964 | Dorothy Mary Crowfoot-Hodgkin is awarded the Nobel Prize in Chemistry |
| 1966 | First successful transplantation of pancreatic tissue by the group of Kelly |
| 1967 | Updike and Hicks realize an implantable miniature electrical transducer of glucose |
| 1970s | Continuous subcutaneous insulin infusion (CSII) |
| 1972 | Introduction of the first standardized U100 insulin |
| 1974 | Development of monocomponent MC insulin or single peak insulin Gérard Slama and colleagues in Paris show that a few days of open-loop intravenous (IV) insulin infusion in type 1 diabetes using a portable pump held in a shoulder bag produce good glycaemic control |
| 1975 | Synthesis of the first fully synthetic insulin CGP 12831 Lowy reports the clinical effectiveness of using SMBG in pregnancy |
| 1978 | David Goeddel and colleagues of the biotechnology firm Genentech use recombinant DNA techniques to produce synthetic “human” insulin Development of the first portable insulin pumps, the Autosyringe, also named ‘Big Blue Brick’ |
| 1979 | Introduction of the first needle-free insulin delivery system by Derata |
| 1980 | Introduction of the “basal-bolus” concept and intensive insulin therapy |
| 1982–1983 | Commercialization of the first insulins utilizing rDNA technology, Humulin® R (rapid) and N (NPH, intermediate-acting) |
| 1983 | Commercialization of the Nordisk infuser |
| 1985 | Novo Nordisk introduces the Insulin Pen delivery system |
| 1988 | Gerald Reaven identifies and describes the constellation of symptoms now called metabolic syndrome |
| 1992 | Medtronic releases the MiniMed 506 insulin pump |
| 1993 | The Diabetes Control and Complications Trial shows the linear relation between the degree of glycemic control and complications Commercialization of the first instant glucose tablets |
| 1996 | Approval of Lispro |
| 2000 | Approval of Aspart |
| 2004 | Approval of Glulisine |
| 2005 | Approval of Detemir Approval of the buccal insulin, Oralin® Approval of the venom of the lizard Gila monster, which contains exendin 4, a molecule fostering one of the insulin-releasing pathways |
| 2006 | Approval of Exubera, the first inhaled insulin |
| 2008 | Approval of the FreeStyle Navigator CGM from Abbott |
| 2013 | Rejection of Degludec The University of Cambridge develops an artificial pancreas that pairs the technology of an insulin pump with a continuous glucose monitor |
| 2015 | Approval of Degludec Dr Edward Damiano introduces the iLet |