Insulin – Its Biochemistry and Physiology

You have surely heard of insulin and glucose because of the frequent articles and discussions on diabetes. If there is one well known hormone that is associated with diabetes it is insulin. Yet exactly what is insulin? Where does it originate from? How does it work? It’s tempting to avoid learning about the biochemistry and physiology of insulin because of its scientific complexity, but having full knowledge is important for better diabetes management.  The more you understand about insulin and glucose, the more control you will have over your body.

What is Insulin?

Insulin is technically a polypeptide hormone. This means it is a compound composed of several molecules held together by peptide bonds. Insulin is called a body regulator because it acts to ensure (regulate) the right amounts of glucose are in the blood stream.[1]

What is its Structure?

Structurally, as noted above, insulin is composed of several molecules that are joined together by peptide bonds. Specifically, insulin is a protein that consists of 2 amino acid chains (alpha chain and beta chain) linked to each by disulfide bonds. If there is a break in the chains, insulin is no longer biologically active.[2]

What is its Origin?

The origin of insulin lies in the pancreas. The average pancreas includes approximately 1 million tiny clusters of cells. Each of these clusters is minute, being no larger than one third of a millimeter in size.  These tiny clusters are called the Islets of Langerhans. The clusters contain four distinctly different and very important types of cells. These are:

  • The beta cells – They comprise approximately 60 % of the total. Beta cells are responsible for the production of both insulin and amylin. Within the secretory glands of the beta cells, you will also find a prohormone that began as an insulin preprohormone when it was attached to the endoplasmic reticulum within the cell.
  • The alpha cells – Their responsibility is the formation of glucagon.
  • The delta cells – This is the smallest portion of cells making up approximately 10% of the Islets of Langerhans. They are responsible for the production of the hormone somatostatin.
  • The gamma cells – They secrete a pancreatic polypeptide.

These different cells, and the hormones they produce, interact. Sometimes the cell activities appear to contradict each other, or one set of cells responds as a reaction to the actions of the other cells. For example, amylin inhibits insulin secretion while insulin hinders the secretion of glucagon, and somatostatin hampers them both.

Insulin – the Hormone

Insulin is the product of the beta cells. The beta cells monitor the circulating glucose in the blood stream. When needed, the beta cells secrete insulin. Once in the bloodstream, insulin has to go to work quickly. It has a half-life of only 6 minutes (half of it is gone within 6 minutes). In fact, most of the hormone has dissipated within the first 12 to 15 minutes. During this time period, the following has happened:

  • Insulin has been absorbed by the target cells
  • Insulin has been degraded by insulinase, a specific enzyme in the liver

The short but productive life of insulin means it is important to be able to control its actions – both being able to turn its production on and off.

Insulin as a Catalyst

By nature and design, hormones are catalysts. Insulin is no different. It sets into motion a specific action while not actually performing the action itself. The trigger setting everything into motion is in its structure. The receptor proteins of insulin on the target cell membrane possess 4 subunits. There are 2 situated on either side of the cell. The insulin molecule binds with the sub units on the cell exterior. Once this occurs, it stimulates an action within the cell membrane. It produces a chain reaction which results in the metabolization of protein, fat and carbohydrates.

The cell reacts swiftly. The response occurs no more than 80 seconds following the action of binding. The result is an increased uptake of glucose by the muscle cells. Concurrently, active means of transport are started. They work to actively convey amino acids, potassium and phosphate ions through what were previously an impermeable cell wall into the interior.

Control of Insulin Secretion

Insulin has a specific control and a designated pathway. It also has certain levels to which it responds. Measurement of insulin levels are based on fasting and non fasting levels. When you are fasting (going without food), with the clinical definition meaning 8 hours free from all carbohydrates, your blood has a glucose level of between 80 and 90 mg/dl. If you measure the insulin level, you will see it is almost nonexistent.[3]

After eating foods that breakdown into glucose, you can measure a rise in the blood sugar level. Blood sugars will typically read at 100-180 mg/dl. As a result, the beta cells immediately work to reduce preformed insulin. The circulating level of insulin rises, accordingly, at a speed of 3 minutes. Yet, the levels of this release quickly decrease by 50% within 10 minutes. After 15 minutes, however, more insulin is released. As a result, the levels climb to a plateau in approximately 60 minutes total. This plateau level does not dissipate quickly. It remains constant for several hours. As soon as the blood glucose level decreases to 100 mg/dl, there is an abrupt stop to the release of insulin. The circulating insulin that remains accordingly falls to a level that is barely noticeable.

Factors Affecting the Production of Hormones

In the production of insulin, there is something called “the anticipatory affect.” This means, that as soon as you ingest food and it enters the stomach, the body is ready and waiting to provide insulin. Before any glucose has even entered into the blood stream, circulating insulin will increase. It is there in preparation for the actual appearance of glucose. This is not the result of the pancreas acting on its own. It is the result of the action of enzymes that reside in the digestive system.[4]

Another interesting fact concerns the productive relationship of certain substances. Research has noted that insulin is not secreted when amino acids enter alone into the blood stream. If, however, amino acids arrive in conjunction with glucose, the amino acids will increase the amount secreted. This is referred to as potentiation. This process acts as a mechanism to aid the metabolism of amino acids as they transverse the cell wall to begin creating the proteins required by the body.

Endocrine Abnormalities, Hormones and Diabetes

Certain endocrine abnormalities have also been associated with diabetes. Among them are gigantism (acromegaly) and Cushing’s disease. The relationship is most likely explained by effect of inadequate hormone production on the insulin secretion of the beta cells. If a person is healthy, the effect is of no consequence. However, if grossly excessive secretion of endocrine hormones occurs, the ability of the beta cells to produce insulin is exhausted. The result may be clinical diabetes.

Conclusion

Insulin is a hormone manufactured within the pancreas. It is one of many responsible for regulating various mechanism of the body. In understanding how it works and what it does, you gain the knowledge needed to prevent becoming diabetic or to manage diabetes through insulin control.

References

[1] Marcovitch, H (2006). Black’s Medical Dictionary 41st edition. Lantham, Maryland: Scarecrow Press.

[2] Murray, R.K;  Bender, DA; Botham, KM; Kennelly, PJ; Rodwell, VW; and Weil, PA (2009). Harper’s Illustrated Biochemistry 28th ed. New York: Lange McGraw Hill.

[3] Guyton, AC; and Hall, JE (2011). Textbook of Medical Physiology, 12th ed. Philadelphia: Saunders.

[4] Meltzer, SJ; and Belton, AB (2009). Diabetes in Adults. Toronto: Key Porter Books.

This article was originally published July 12, 2012 and last revision and update of it was 9/10/2015.