The discovery of insulin in 1922 marked a major breakthrough in medicine and therapy in patients with diabetes. Long before the discovery of insulin, it was hypothesized that the pancreas secreted a substance that controlled carbohydrate metabolism. For years, attempts at preparing pancreatic extracts to lower blood glucose were unsuccessful due to impurities and toxicities. Eli Lilly began producing insulin from animal pancreas but fell short of the demand, and the potency varied up to 25% per lot. In 1978, the first recombinant DNA human insulin was prepared by David Goeddel and his colleagues (of Genentech) by utilizing and combining the insulin A- and B- chains expressed in Escherichia coli. Thereafter, Genentech and Lilly signed an agreement to commercialize rDNA insulin. In 1982, the first insulin utilizing rDNA technology, Humulin® R (rapid) and N (NPH, intermediate-acting), were marketed. Currently, there are two basal insulin analogs in the market, glargine, approved in 2000, and detemir, approved in 2005. Glargine has glycine instead of asparagine at position A21, an extra two arginine molecules at position B30 and a pH of 4.0. It forms microprecipitates at the site of injection resulting in a prolonged absorption with little peak activity. Here you have a recent crystal structure of B30 insulin determined by X-ray crystallography and showing the typical hexameric arrangement of insulin monomers (PDB code: 7JP3)

#molecularart ... #immolecular ... #insulin ... #B30 ... #diabetes ... #hexamer ... #crystal ... #xray

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Insulin B30
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Insulin B30

Published: