Insulin analogue

An insulin analog is an altered form of insulin, different from any occurring in nature, but still available to the human body for performing the same action as human insulin in terms of glycemic control. Through genetic engineering of the underlying DNA, the amino acid sequence of insulin can be changed to alter its ADME (absorption, distribution, metabolism, and excretion) characteristics. Officially, the U.S. Food and Drug Administration (FDA) refers to these as "insulin receptor ligands", although they are more commonly referred to as insulin analogs.

These modifications have been used to create two types of insulin analogs: those that are more readily absorbed from the injection site and therefore act faster than natural insulin injected subcutaneously, intended to supply the bolus level of insulin needed at mealtime (prandial insulin); and those that are released slowly over a period of between 8 and 24 hours, intended to supply the basal level of insulin during the day and particularly at nighttime (basal insulin). The first insulin analog approved for human therapy (insulin Lispro rDNA) was manufactured by Eli Lilly and Company.

Eli Lilly and Company developed and marketed the first rapid-acting insulin analogue (insulin lispro rDNA) Humalog. It was engineered through recombinant DNA technology so that the penultimate lysine and proline residues on the C-terminal end of the B-chain were reversed. This modification did not alter the insulin receptor binding, but blocked the formation of insulin dimers and hexamers. This allowed larger amounts of active monomeric insulin to be available for postprandial (after meal) injections.

Novo Nordisk created "aspart" and marketed it as NovoLog/NovoRapid (UK-CAN) as a rapid-acting insulin analogue. It was created through recombinant DNA technology so that the amino acid, B28, which is normally proline, is substituted with an aspartic acid residue. The sequence was inserted into the yeast genome, and the yeast expressed the insulin analogue, which was then harvested from a bioreactor. This analogue also prevents the formation of hexamers, to create a faster acting insulin. It is approved for use in CSII pumps and Flexpen, Novopen delivery devices for subcutaneous injection.

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