Hormone replacement therapies Insulin

Currently research is being carried out into the suitability of the nasal route for the administration for drugs for insulin-dependent diabetes and hormone replacement therapy. 

Biotechnology has provided hormone replacement therapy with the introduction of human insulin (66,67,68), the first U.S. FDA-approved rDNA drug in 1982, for the treatment of insulin-dependent diabetes. The human insulin molecule has the structural characteristics of a large protein yet is only the size of a polypeptide, totaling 51 amino acid residues. Two disulfide bonds (cysteine [Cys] A7 to Cys B7 and Cys A20 to Cys B19) link two... 

Insulin is used in the replacement therapy of diabetes mellitus to supplement a deficient secretion of endogenous hormone. 

Rosenfalck AM, Maghsoudi S, Fisker S, Jorgensen JO, Christiansen JS, Hilsted J, Volund AA, Madsbad S. The 68. effect of 30 months of low-dose replacement therapy with recombinant human growth hormone (rhGH) on insulin... 

Replacement Therapy. If the endogenous production of a hormone is deficient or absent, therapeutic administration of the hormone can be used to restore normal endocrine function.30 35 The exogenous hormone can be obtained from natural sources, such as extracts from animal tissues, or from chemical synthesis. In addition, new recombinant DNA techniques are being used to produce hormones from cell cultures, and these techniques have shown great promise in being able to generate hormones like human insulin. 

For the first time in history there was clear, unambiguous clinical evidence, in humans, that symptoms of diabetes mellitus could be controlled with the exogenous administration of the active factor of the pancreas—insulin. Thus, replacement therapy with the newly discovered hormone, insulin, had arrested what was clearly an otherwise fatal metabolic disorder. From that point forward, diabetes mellitus (type 1) became a manageable disease by pharmacological intervention. 

Although replacement therapy is basically limited to endocrine disorders, it still plays an important therapeutic role in clinical pharmacology. The number of people requiring replacement therapy for diabetes and hypothyroidism alone makes insulin and thyroid hormone among the most commonly prescribed drugs in the United States. For example, the drug Synthroid is taken daily by 8 million people to correct hypothyroidism, and its share of the market is worth 600 million per year. As more information is discovered about the role of other endogenous substances in the body, new examples of replacement therapy will occur. 

Insulin is isolated from beef and pork pancreas. However, human insulin is replacing the animal hormone for therapy. Human insulin is produced by a special strain of Escherichia coli that has been genetically altered to contain the gene for human insulin. Pork insulin is closest in structure to human insulin, differing by only one amino acid. 

Endogenous substances given essentially as replacement therapy (i.e., physiological levels), particularly where there is previous clinical experience with similar products (e.g., animal insulins, pituitary-derived growth hormone, and calcitonin). 

In many cases the most important aspect of structural studies is that knowledge of the structure of a protein leads to improved understanding of its function. For instance, if a protein has to be administered for lifetime or longterm replacement therapy (e.g., insulin, growth hormone, factor IX), it is important to know all about its structure-function-stability relationships. A longer turnover time or a higher specific activity, for example, allows for a smaller dose to be administered, which has medicinal and financial benefits. 

The therapeutic use of homologous human proteins - including insulin, growth hormone, and colony stimulating factors - in replacement therapy, has been adequately supported by subchronic toxicity studies in animal species reactive to their pharmacological or physiological effects. Extension to chronic studies has usually not provided valuable additional safety information. 

As mentioned in Chapter 1, perhaps the purest form of drug therapy is the replacement of inadequate amounts of an endogenous substance such as a hormone. Any gland that normally secretes a hormone is a potential target for hypofunctioning. Classical examples include Addison s disease (adrenal cortex), dwarfism (anterior pituitary), juvenile-onset insulin-dependent diabetes (pancreas), and hypothyroidism (thyroid). 

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