Understanding the Chemistry of Insulin
Editor’s Note: This article was originally written by patient expert Anna.
Even though I take insulin every day, I never considered the chemistry of insulin until I began working in a chemistry research lab at college. Prior to this year, the sum of my knowledge about insulin probably came from one of those “Newly Diagnosed” pamphlets that the doctors were so quick to administer in the first few appointments. I knew that, like all Type I diabetics, my body no longer produced insulin. Insulin, I learned, is the key hormone needed to regulate energy and glucose metabolism.
Insulin is a polypeptide hormone, which means that is it composed of two protein strands. Proteins are molecules composed of smaller subunits called amino acids, which join together through a peptide bond. Long chains of amino acids fold in a very particular way, forming mature and functional proteins. Proteins have many important functions in the body, including structure, immune defense, and transport. Certain proteins function as hormones, as in the case of insulin.
Insulin is important in regulating levels of blood glucose and providing energy to all tissues. In the body, dietary carbohydrates are broken down into a simple sugar, glucose, which is transported in the blood. In response to the spike in blood glucose levels, the pancrease releases insulin as part of a negative feedback system to maintain homeostasis. Insulin lowers blood glucose levels by facilitating the sugar molecules from carbohydrates to leave the bloodstream and enter energy-starved cells.
The specific cells that produce insulin are the Î²-cells of the islets of Langerhans in the pancreas. A mature insulin molecule contains two chains- an A and a B chain, held together by disulfide bonds. In the Î²-cells, insulin is first transcribed as preproinsulin, which is transformed into proinsulin. The center portion of the sequence, known as C-peptide, is then removed, leaving a mature insulin molecule. Although insulin can be found in the body in three forms, hexamer, dimer, and monomer, the monomeric form of insulin is the most active and the only form that may be absorbed by energy-starved cells.
Insulin was first discovered and linked to diabetes in 1922 by Frederick Banting and Charles Best. For the first time, diabetic patients could be treated with insulin therapy. Yet, until the 1980s, these patients took bovine or pig insulin, which had slightly different amino acid sequences and were commonly contaminated with foreign proteins, resulting in unreliable activity and induced immune responses.
Aiming to solve these problems, decades of research was focused on enhancing the purity of extracted insulin and prolonging the duration of action of the administered insulin. Eventually, scientists looked to the in vitro production of human insulin using Escherichia coli bacteria.
Today, human insulin is sold in the form, Humulin ®, which is produced by Eli Lilly and Co. There are also a variety of insulin mixtures available commercially, which contain both quick-acting insulin (such as Humalog ® and Novolog ®) and Humulin ®, allowing for both short- and long-lasting use.
I use Humalog ® insulin in my pump. The active ingredient in Humalog ® is Lispro, which is produced by Eli Lilly. Lisopro is identical to human insulin, except the two amino acids in the 28th and 29th positions of the B chain are reversed. While a proline and a lysine residue occupy the 28th and 29th spot in naturally occurring human insulin, the lysine precedes the proline in Humalog ®. This small difference is important because it has been shown to diminish the formation of inactive insulin dimers and aggregates.
Although the quality of insulin therapy has improved greatly since its discovery, it is not a cure for diabetes. Instead, insulin therapy is a means of survival, a temporary life support, until a permanent cure is found. The next step for scientists is to utilize embryonic stem cells for pancreatic cell implantation.