Insulin discovery

Roseneeld, L. (2002). Insulin discovery and controversy. Clin. Chem. 48, 2270-2288. 

Pulmonary delivery of insulin for systemic absorption in the treatment of diabetes has been studied extensively since the early days of insulin discovery almost a century ago. Colthorpe et al. and Pillai et al. demonstrated in rabbit and monkey models, respectively, that the deeper into limg the dose of insulin was delivered, the higher was the bioavailability. The work of Laube, Benedict, and Dobs showed the need to achieve deep pulmonary deposition of this molecule for efficient absorption in humans. Handheld liquid and dry powder delivery systems have been developed to generate insulin-containing aerosols with the majority of the particles in the aerodynamic size range 1-3 pm. The relative bioavailability compared with subcutaneous injection based on the insulin contained in the dosage form was 110/ [52] powder system and for the aqueous-based... 

Rosenfeld, L. (2002) Insulin Discovery and controversy. Clinical Chemistry, 48,2270-2288. 

M. Bhss, The Discovery of Insulin, University of Chicago Press, Chicago, 1982. 

Calpain-10 (CAPN10) is the fust diabetes gene to have been identified through a genome scan. The discovery of calpain-10 has identified it as a molecule of importance to insulin signaling and secretion that may have relevance to the fiiture development of novel therapeutic targets for the treatment of type 2 diabetes. 

Science and civilisation in China. Volume 5. Chemistry and chemical technology. Part HI Spagyrical discovery and invention Historical survey, from cinnebar elixirs to synthetic insulin, by Joseph Needham, Ho Ping-Yu, Lu Gwei-Djen and Nathan Sivin. Cambridge Cambridge Univ P, 1976. 

Chemists commonly use a process called X-ray diffraction to determine the structure of a compound. Two pioneers of X-ray diffraction were Rosalind Franklin and Dorothy Crowfoot Hodgkin. Franklin s work on the DNA molecule was instrumental in the discovery of its helical shape. Nobel Prize winner Hodgkin discovered the structure of complex molecules, such as cholesterol, penicillin, insulin, and vitamin B-12. Find out about X-ray diffraction how it works and the types of scientists who employ this technology. 

The discovery of insulin is one of the great stories in human medical history. I think it is well worthwhile to provide a brief account of the discovery of this hormone and its impact on human health before we proceed with our story about proteins in general. 

In 1982, Michael Bliss published an intimately detailed history of the discovery of insulin, updated in 2007 The Discovery of Insulin 25th Anniversary Edition The opening words of this book follow ... 

The discovery of insulin at the University of Toronto in 1921-22 was one of the most dramatic events in the history of the treatment of disease. Insulin s impact was so sensational because of the incredible effect it had on diabetic patients. Those who watched the first starved, sometimes comatose, diabetics receive insulin and return to life saw one of the genuine miracles of modem medicine. They were present at the closest approach to the resurrection of the body that our secular society can achieve, and at the discovery of what has become the elixir of life for millions of human beings around the world. 

Except for a veiled but important reference in Banting s 1922 account, there are no other useful written records of this incident. Clark Noble once drew a cartoon, unfortunately now lost, of Banting sitting on Collip, choking him he captioned it The Discovery of Insulin . 

The discovery of vinblastine and vincristine is one of the most intriguing examples of serendipity in scientihc research in recent years. In 1952, the Canadian medical researcher Robert Laing Noble (1910-90) received a package from his brother. Dr. Clark Noble, containing 25 leaves from the Madagascar periwinkle plant. Vinca rosea. Clark had received the leaves from one of his patients in Jamaica, who said that natives on the island often used the plant to control their diabetes when insulin was not available. Clark, who was retired, suggested that his brother study the plant for possible use as a drug for the treatment of diabetes. 

Many successful protein products, including antibodies, have been marketed over the years for the treatment of a number of diseases. One of the oldest examples of a protein product is insulin, still one of the most successful drugs after 70-80 years of its discovery. Early insulin preparations, derived from natural sources, are being replaced by recombinant human insulin preparations and new formulations are being marketed that provide a more gradual and continuous release profile and maximise glucose control in diabetic patients. " ... 

In comparison to the level of cellular serine or threonine phosphorylation, protein tyrosine phosphorylation occurs at quite low levels in normal cells but dramatically increases upon oncogenic transformation or stimulation. Since the first discovery in 1978 that the transforming protein from Rous sarcoma virus (pp60vsrc) exhibited intrinsic kinase activity/5 protein kinase activity has also been shown to be inherent to other growth factor receptors such as epidermal growth factor receptor and the insulin receptor,[6 91 and to involve autophosphorylation processes. The diverse biochemical activity exhibited by protein tyrosine phosphorylation has stimulated the development of chemical methods for the preparation of phosphorylated peptides for use as substrates in elucidating the biochemical and physiological activity of phosphorylated site(s). 

Insulin Preparations. Since diabetes mellitus is a defect of one or more of insulin production, secretion, or action, the administration of insulin replacement as a treatment for diabetes in the 1920s was a landmark discovery. Historically, most commercial insulin came from either bovine or porcine sources. Beef insulin differs from human insulin by three amino acid substitutions pork insulin differs by only one residue. For many years, standard insulin preparations were 70% beef and 30% porcine. However, the biosynthesis of human insulin has now displaced the animal insulins, especially bovine insulin which was more antigenic. Mass production of human insulin by recombinant DNA methods is achieved by inserting the human proinsulin gene into either E. coli or yeast and treating the resulting proinsulin to yield the human insulin molecule. Insulin preparations may be divided into four major types ... 

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