Insulin is a naturally occurring hormone produced by the pancreas, regulating blood sugar levels by allowing glucose to enter cells for energy. Millions of individuals living with diabetes rely on manufactured insulin to manage their condition, as their bodies either do not produce enough insulin or cannot effectively use the insulin they do produce.
Early Insulin Production
For many years, insulin used to treat diabetes was sourced directly from the pancreases of animals, primarily cows and pigs. Animal-derived insulin was life-saving but presented challenges. Issues with purity were common, and some patients experienced allergic reactions to these foreign proteins. The logistical demands of securing a consistent, large-scale supply from animal organs became increasingly difficult as the number of people requiring insulin grew.
The Rise of Recombinant DNA
The limitations of animal-sourced insulin spurred a search for alternative production methods, leading to a revolutionary scientific advancement: recombinant DNA technology. This breakthrough involves isolating a specific gene, such as the human gene responsible for producing insulin, and inserting it into the genetic material of another organism. Typically, this host organism is a fast-growing microbe like Escherichia coli bacteria or yeast. The modified microorganisms then act as tiny biological factories, replicating and producing the desired human protein. This technological shift was transformative for insulin production, enabling the creation of insulin identical to that produced by the human body, which reduced allergic reactions and inconsistencies while enabling scalable manufacturing to meet global demand.
Modern Insulin Manufacturing
The current production of insulin begins by obtaining the specific human gene that codes for insulin. This gene is then inserted into a small, circular piece of bacterial DNA called a plasmid. Restriction enzymes are used to cut both the human insulin gene and the plasmid, creating complementary “sticky ends” that allow the two DNA pieces to join together. The human insulin gene is then ligated into the opened plasmid using an enzyme called DNA ligase, forming a recombinant plasmid.
These recombinant plasmids are then introduced into host cells, commonly E. coli bacteria or yeast, through a process called transformation. The transformed cells are subsequently cultured in large, controlled environments known as bioreactors. Within these bioreactors, the host cells multiply rapidly and, guided by the inserted human gene, begin to produce proinsulin, a precursor molecule to active insulin.
Once proinsulin is produced, the cells are harvested, and the proinsulin is extracted. Proinsulin is then enzymatically converted into active human insulin. This involves removing a connecting peptide (C-peptide) from the proinsulin molecule, leaving behind the two functional insulin chains, A and B, which are held together by disulfide bonds. Initial purification steps separate the insulin from cellular debris and byproducts.
Quality Control and Formulation
Quality Control
After the initial production and purification, the insulin undergoes stringent quality control measures and extensive testing. These checks confirm purity, potency, and safety, ensuring it is free from contaminants and maintains correct concentration. Stability tests ensure the product remains effective over its shelf life.
Formulation
Once these quality checks are complete, the purified insulin is prepared into various formulations. Different types of insulin, such as rapid-acting, short-acting, intermediate-acting, or long-acting versions, are created to meet specific patient needs by altering absorption rates. The insulin is then packaged into vials, pens, or cartridges, ready for distribution to patients worldwide.