The treatment of Diabetes, the deadly disease of all times, is made possible only after the historic discovery of the most effective drug, Insulin. It was a milestone and has truly revolutionized both therapy and prognosis of diabetes.
Insulin is a peptide hormone, which is produced and released by beta cells of the pancreatic islets, that finely tunes the metabolism of carbohydrates, fats and protein inducing the uptake of glucose from the blood into fat, liver and skeletal muscle cells.
HISTORY
The term “diabetes mellitus” was introduced in 1674 by the British physician Thomas Willis of the Iatrochemical School of medicine, for clinically differentiating this disease from the diabetes insipidus, referring to the particular sweetness of urine in diabetic patients. Willis defined diabetes mellitus as the “Pissing Evil”.
The Indian physician, Sushruta, and the surgeon Charaka were able to distinguish between a diabetes type 1 and a diabetes type 2, termed as “madhumeha” (‘honey urine’).
In 1869, the German pathologist, physiologist and biologist Paul Langerhans announced that pancreas has two systems of cells –Alpha cells and Beta cells.
In 1910, in London, Sir Edward Albert Sharpey- Schafer described that the pancreatic islands are able to secrete a substance capable of controlling glucose metabolism, which he termed “insulin,” from Latin “insula” (“island”), with reference to the Langherans islands.
Another important scholar in the history of insulin discovery is Paulescu, who called it “pancreas”. He studied medicine in Paris had described in depth the clinical differences between diabetes type 1 and type 2 in 1876.
BANTING
In 1920, Banting, a young Canadian orthopedic surgeon who served as a medical officer in England and in France, on studying the work by Moses Barron entitled “The relation of the Islets of Langerhans to Diabetes” was struck by the description on the binding of the pancreatic ducts in rabbits, dogs and cats, in order to study the relationship between pancreas and diabetes.
Banting was also impressed by the work of E.L. Scott, who, in 1912 came almost to the discovery of insulin, using an alcohol extract, which led him to a step away from the discovery of insulin.
The difficulty of all scholars was to separate the extract of the Langerhans islands from the rest of the pancreatic exocrine tissue. Banting at the University of Toronto succeeded in this.
Since November 1920, Banting began working in a laboratory led by John James Richard MacLeod, to isolate the hormone secreted by the pancreatic islands. MacLeod allowed Banting to be assisted by two young assistants, Best and Noble. The researchers closed the pancreatic ducts with a technique designed by Banting to get the degeneration of the pancreatic exocrine tissue and to obtain a pancreatic islet from the pure state. With this liquid extract, for the first time, in the history of medicine, Banting and Best found the way to control glucose in a diabetic animal.
MacLeod, guessed the historical importance of the results and, on 11th January 1922, he authorized to conduct experimentation in humans.
CLINICAL TRIALS
Leonard Thompson, a 14-year-old, serious diabetic patient at the Toronto General Hospital, was the first patient to be treated. However, the initial clinical experimentation was a failure. On January 23rd Leonard underwent another series of injections and this time he experienced a normalization of glycaemia, glycosuria, and ketonuria. The merit was also of the clinical biochemist James Bertram Collip, who developed a new extraction and concentration protocol.
Besides Leonard, Joe Gilchrist, a diabetic doctor, was another patient who underwent the innovative treatment, and was also the first patient to suffer from hypotensive hyperglycaemia, one of the side-effects of insulin therapy.
On the basis of these successes, on 12th December 1921, Banting and Best reported the results of the discovery of insulin to the American Society of Physiology.
In 1923, a German pharmaceutical firm began producing insulin with the manufacturing license issued by the Toronto Insulin Committee.
In 1923 Banting and MacLeod were awarded the Nobel Prize for Physiology or Medicine.
After 1921, scholars intensified their efforts to obtain pure and crystalline insulin preparations.
Banting and Best had obtained short-acting insulin preparations, lasting about 6 h, with inevitable and subsequent peaks of hyperglycaemia and glycosuria, within 24 h. The efforts lead to the production of a delayed-acting insulin to counteract both hyperglycaemia and hypoglycaemia.
In 1963 and 1965, independently P.G. Seeing in the USA, Wangyu in the Popular Republic of China and H. Zahn, in Western Germany were able to synthesize insulin.
In 1975, fully synthetic insulin (CGP 12 831) was synthesized in the laboratories of Ciba-Geigy in Basel.
In 1996, Eli Lilly introduced the first type of analog insulin lispro under the brand name of Humalog.
Exubera, the first inhaled insulin, has been developed by Sanofi-Aventis and Pfizer and marketed by Pzifer in 2006.
Another promising product is the buccal/oral insulin. Oralin was approved in 2005 in Ecuador and marketed by Generex uses RapidMist technology to deliver a mixture of insulin, surfactants and lipids to buccal mucosa.
The developments are still on for more safe and effective Insulins for containing Diabetes.
