Insulin by recombinant DNA technology

Human insulin produced by recombinant DNA technology was first approved for general medical use in 1982, initially in the USA, West Germany, the UK and The Netherlands. As such, it was the first product of recombinant DNA technology to be approved for therapeutic use in humans. From the 1990s on, several engineered insulin products (discussed later) also gained approval (Table 11.3). 

A wide range of pharmaceutical substances are derived from animal sources (Table 1.10). Many are protein-based and detailed description of products such as insulin and other polypeptide hormones, antibody preparations, vaccines, enzymes, etc., have been deferred to subsequent chapters. (Many of the therapeutic proteins are now also produced by recombinant DNA technology. Considerable overlap would have been generated had a product obtained by direct extraction from native sources been discussed here, with further discussion of a version of the same product produced by recombinant DNA technology at a later stage.) Non-proteinaceous pharmaceuticals originally derived from animal sources include steroid (sex) hormones, corticosteroids and prostaglandins. A limited discussion of these substances is presented below, as they will not be discussed in subsequent chapters. Most of these substances are now prepared synthetically. 

Human insulin B.P.jEur.P. insulin of human sequence produced either by enzymatic modification of porcine insulin or by recombinant DNA technology... 

Biopharmaceuticals are protein macromolecules, usually prepared by recombinant DNA technology, which are used as therapeutics. This group includes replacement hormones such as insulin, cytokines such as interferons, and monoclonal antibodies. 

Most of the insulins derived from beef and pork have been largely replaced by the human form, synthesized utilizing recombinant DNA technology. For example, lispro insulin is synthesized by recombinant DNA technology, using a non-pathogenic strain of E. coli. 

Baker, R. S., Schmidtke, J. R., Ross, J. W., and Smith, W. C. (1981). Preliminary studies on the immunogenicity and amount of Escherichia coli polypeptides in biosynthetic human insulin produced by recombinant DNA technology. Lancet 2(8256), pp. 1139-1142. 

Human insulin was the first commercial health care product produced by recombinant DNA technology ZjEliJLilly,.the producer of this synthetic insulin, often relied on HPLC to confirm the structure and to determine the potency of synthetic human insulin. The story behind Lilly s recombinant DNA-produced insulin is described in an article in Science (1) High performance liquid chromatography (HPLC) techniques developed at Lilly can detect proteins that differ by a single amino acid, and HPLC tests show human insulin (recombinant DNA) is identical to pancreatic human insu-... 

Insulin is an amphoteric pancreatic protein which is extracted from beef or pork pancreas and purified by crystallisation. Insulin which is structurally identical with human insulin may be produced by chemical manipulation of animal insulin or by recombinant DNA technology. 

Insuhn is a protein hormone produced by the (5-ceUs of the islets of Langerhans in the pancreas. Insulin was the first protein hormone to be sequenced, the first substance to be measured by radioimmunoassay (RIA), and the first compound produced by recombinant DNA technology for practical use. It is an anaboUc hormone that stimulates the uptake of glucose into fat and muscle, promotes the conversion of glucose to glycogen or fat for storage, inhibits glucose production by the liver, stimulates protein synthesis, and inhibits protein brealcdown. 

Human insulin (humulin) is prepared by recombinant DNA technology or is synthesized from porcine insulin (enzymatic replacement of the terminal arginine with threonine). Human insulin is preferred to insulin prepared from animals because it is less antigenic. Porcine insulin differs from human insulin by one amino acid (terminal arginine). Bovine insulin is the most immunogenic preparation. A typical dosing... 

Much has been learned about insulin because of its relationship with diabetes. In classical, type I diabetes (or insulin-dependent diabetes), the individual does not make insulin, or at least not enough of it. This is usually caused by destruction of the beta cells of the islets of Langerhans in the pancreas from a type of autoimmune disease. The only remedy for type I diabetes is regular insulin injections, and insulin is produced for this purpose by recombinant DNA technology (Chapter 13). 

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