The Chemistry of Insulin Apart

Introduction

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Insulin is an amazing drug that is used to help diabetic people live as healthy lives as they can. The drug is injected by syringe after a diabetic person eats, replacing the natural process that occurs in nondiabetic people, where insulin is transferred from the pancreas to the bloodstream into cells to take the new sugar and use it for energy or later use. Novolog, or insulin aspart, a specific type and brand of insulin, works in its own specific way. Insulin aspart is called rapid-acting insulin, in which the composition is manipulated from normal insulin to make it work faster. Insulin aspart starts to work 15 min after it is injected.

I chose to do insulin, specifically insulin aspart, because I have been a type 1 diabetic for 8 years and use it everyday. Before researching, I was interested in how close man-made insulin was to human insulin, and it turns out that they are almost identical, being only one amino acid different. Insulin has always fascinated me. Insulin has affected my life in great ways. It is the single reason that I am still alive and healthy. Without it, especially insulin aspart, I do not even want to image what my life would look like, or what could ever take its place.


Composition of ...

  • C256H381N65O79S6     

    • 100 Units/mL

      • Zinc = 19.6 mcg/mL

      • Disodium hydrogen phosphate dihydrate = 1.25 mg/mL

      • m-Cresol = 1.72 mg/mL

      • Phenol = 1.5 mg/mL

      • Glycerin = 16 mg/mL

      • Sodium Chloride = .58 mg/mL

      • Water = remainder for injection


Main Chemicals, Compounds, Components

  • Glycerin = C3H8O3

Glycerin is a simple sugar alcohol compound that is used in insulin as an isotonicity agent, or thing that makes insulin flow inside a body, like water. It is also a humectant, which means that it keeps insulin in liquid form for longer. Glycerin is a very important part of insulin aspart because it allows for the insulin to be injected smoothly and with little pain and metabolize faster. Glycerin is added into the insulin mix when the powder form of insulin, which insulin is in to keep it safe to use for longer, is being rehydrated into a liquid for use.

  • m-Cresol = C7H8O

M-Cresol, or 3-methylphenol, is a colorless, viscous liquid that is essential to lots of chemical production as a preservative. Before insulin can be drawn from a vial, an equal amount of air must be pushed into the vial. That air can be contaminated with bacteria. Preservatives must be used to kill that bacteria to prevent transmitting infection through the insulin injection site. A little air can get into the vial of an insulin pen, so it requires some preservatives. M-Cresol is added during rehydration, just like glycerin.


Chemistry's Role

Chemistry plays an integral role in the the making and functions of insulin aspart. Insulin works as a key that unlocks the body’s cells in order to take the sugar, or glucose, within, and make it into energy. If insulin is not present in a body, then bloodsugar, or the sugars in your bloodstream that get there from the food we eat, is too high for the body to function correctly. Basically, insulin is the inducer for a chemical reaction to happen inside the body so that sugar is used properly in our cells. When it comes to the making of insulin aspart, (which will be further explained in the Background Research section), chemicals and chemical reactions are the foundation of the creation process. The chemicals that are included in the making of insulin are zinc, disodium hydrogen phosphate dihydrate, m-Cresol, phenol, glycerin,  and sodium chloride. There are even more chemical reactions involved in the making of insulin aspart. The first of these chemical reactions is called insulin analogs, where scientists take animal insulin and tweak its amino acid chain to be more similar to human insulin. Another one of these chemical reactions is the genetic modification of E. Coli, a bacteria, to make it safe for use and the genetic modification of saccharomyces cerevisiae, a type of yeast. A centrifuge is also used, which is a machine that uses force to separate particles of different densities. Lastly, enzyme mixes are used, which are a mix of proteins that act as catalysts in biological systems.

Background Research

Insulin, in its modified form, has only been around since 1922. Back in that time, it took around 2 tons of pig pancreases to make an 8 oz. purified bottle of insulin, and only one type was available: fast-acting insulin, like insulin aspart. In all of those years, even though pigs are no longer needed nearly as much, insulin aspart has been man-made and chemistry is used in the entire process of making it, from start to finish. Since animal insulin is rejected by the human body, lots of steps are needed to make the final form. The first process is insulin analogs. Then, scientists take half a gram of a genetically modified strain of E. Coli and add it to a genetically modified strain of saccharomyces cerevisiae (a type of yeast). The microorganisms then begin to grow rapidly. Next, water, sugar, and nitrogen are added and so is ampicillin, which is added to eat off everything but the needed protein producers. Then, a chemical called an inducer is added to the mix of bacteria. Next, the bacteria critters begin making insulin by holding the protein clumps inside themselves. Then, you have to separate the insulin from the mound of now trash bacteria using a centrifuge, which is basically a chemical separation machine. That new broth is then replaced with a liquid containing a substance that breaks down cell membranes, helping release the insulin from the bacteria. Insulin at this point still isn't insulin, but proinsulin, an inactive precursor of insulin. Scientists then use an enzyme to carve out the proinsulin, leaving behind the 51 insulin enzymes. Then, the insulin is separated from other molecules based on their electrical charge, acidity, size, and other characteristics. After that process, the insulin is pure, but inactive. So to fix this, scientists use another enzyme mix to iron out the wrinkles and get the insulin in its final form. The final step in crystallization. The insulin is mixed with zinc, which helps form stable crystals, and dried until its nothing but powder of crystals. When needed, the crystals are rehydrated and made into liquid form for use.

As for glycerin and m-Cresol, both are made in a lab and added to the final liquid form of insulin when it is rehydrated for use. To make glycerin, you first have to prepare animal fat for rendering. Then, you render the tallow. Next, you prepare the lye solution and cool the tallow. Then, you have to ensure that the ingredients that you have are ready to be mixed. Next, you mix, add salt, remove the syrup, and strain the glycerin. Glycerin is not naturally occurring and can only be made in a lab, but anyone can make it. As for m-Cresol, it is first together with many other compounds, and then extracted from coal tar, and gathered from the residue of making coke to tar. The residue contains a few percent by weight of phenol and multi-compound cresols. In the next process, phenol is alkylated (chemicals are added) with propylene to give isomers of cymene. In layman's terms, this basically means that m-cresol is extracted from coal in small amounts and then chemicals are added and  complicated chemical processes happen and m-Cresol is created. The only place that you can find m-Cresol outside of a lab is in the temporal gland secretions during testosterone rushes in male african elephants.


Resources

http://www.endocrineweb.com/conditions/type-1-diabetes/what-insulin

  • Explains what insulin is

  • Says all of the different kinds of insulin

https://www.ghc.org/popup.jhtml?item=/common/healthAndWellness/conditions/diabetes/insulinProcess.html

  • Explains the basis of how insulin works in the body

http://www.diabetes.org/living-with-diabetes/treatment-and-care/medication/insulin/insulin-basics.html?referrer=https://www.google.com/

  • Explains the basics of what insulin is and how it works

http://www.webmd.com/diabetes/guide/diabetes-types-insulin

  • Explains the length of time it takes for insulin aspart to work

https://en.wikipedia.org/wiki/Insulin_aspart

  • All the parts, pieces, and components of insulin aspart

  • Resource for other web links

http://www.yourdictionary.com/centrifuge

  • Centrifuge machine definition

http://www.drugbank.ca/drugs/DB01306

  • Insulin aspart description

  • Chemical formula

http://www.diabetesforecast.org/2013/jul/making-insulin.html?referrer=https://www.google.com/

  • How insulin is made

https://en.wikipedia.org/wiki/Glycerol

  • All information on glycerol

http://ksupc.com/download/xArchive/level9/427/Sterile%20products/Lab/ISOTONICITY.pdf

  • Definition on isotonicity

http://care.diabetesjournals.org/content/6/4/387.abstract

  • What glycerol does for insulin

https://en.wikipedia.org/wiki/M-Cresol

  • All information of m-Cresol

http://www.wikihow.com/Make-Glycerin

  • How glycerin is made

http://www.bd.com/us/diabetes/page.aspx?cat=7001&id=7244

  • How insulin works inside of a diabetic person's body

    • Blood sugar regulation

http://www.medicalnewstoday.com/articles/249413.php

  • Definition of bloodsugar

  • Definition of blood glucose

About the Author
Sidney Bennett is a junior at Billings Senior High School. She is a type 1 diabetic and uses insulin aspart in her everyday life. She is involved with cheerleading, senior advocates, teen council, and lots of different volunteer organizations, all revolving around kids. She works as a lifeguard and swimming lessons teacher. She plans to attend college in Seattle, Washington after high school to pursue a career in pediatric medicine.
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