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Biology · Ch 10 — Biotechnology and its Applications

Human Insulin Production

10.10

Human Insulin Production

Human insulin is a small protein hormone, produced naturally by beta cells in the pancreas, that regulates blood glucose levels; a deficiency or malfunction in insulin production or action causes diabetes mellitus. Before recombinant DNA technology became available, insulin used to treat diabetic patients was extracted and purified from the pancreases of slaughtered cattle and pigs.

This animal-derived insulin created two significant problems. First, although it was effective at lowering blood glucose, animal insulin differs from human insulin by a small number of amino acids, and this slight structural difference caused some patients to develop allergic reactions or immune responses against the foreign protein over time, reducing its effectiveness and sometimes causing harmful side effects. Second, because it depended entirely on the supply of animal pancreases from the meat industry, animal-derived insulin was produced in limited quantities and at relatively high cost, which was a growing concern as the number of diabetic patients requiring lifelong insulin treatment increased worldwide.

Human insulin, as it occurs naturally in the body, is a small protein made of two short polypeptide chains -- chain A and chain B -- held together by two disulphide bonds (chemical bridges formed between sulphur atoms), with a third disulphide bond within chain A itself. In the human pancreas, insulin is initially synthesised as a single longer precursor molecule called proinsulin, which contains an additional connecting segment, called the C peptide, between what will become the A and B chains; this C peptide is subsequently cut out and removed, leaving the mature, two-chain, disulphide-linked insulin molecule. …