Insulin is perhaps the most important compound circulating in our bodies. It is involved in more than 60 key biological processes. Impairments in insulin function affect many facets of health and well-being and, if left uncorrected, are ultimately fatal. Despite its paramount importance, the functions of insulin in the body are widely misunderstood.
Insulin is an anabolic hormone, meaning it acts to promote synthesis and building, as opposed to catabolic hormones that break down and deconstruct bodily tissues and compounds. Given its vital importance, it is curious that insulin is sometimes portrayed as the bad guy. Consider, for instance, how we cast insulin as the villain responsible for the development of adverse health conditions: type 1 and type 2 diabetes, metabolic syndrome, polycystic ovary syndrome, and even certain types of cancer.
In this article, we will explore the basic functions of insulin in the body to gain a better appreciation for all it does as well as a clearer understanding of how to keep this hormone functioning in balance and at its optimal capacity.
What Is Insulin?
In technical terms, insulin is a peptide hormone produced by pancreatic beta cells located in the islets of Langerhans. As touched on in the introduction, insulin is the primary anabolic hormone found in the human body.
It governs the metabolic processes your body uses to digest and absorb carbohydrates, proteins, and fats, playing a particularly prominent role in the absorption of carbohydrates—specifically, the movement of glucose from the bloodstream into the liver, muscle, and fat cells throughout the body. Insulin acts on receptors located on the membranes of cells in the liver, other organs, and muscles to promote the uptake of glucose from the blood into the tissue where it is used as fuel or stored as glycogen for later use. Once insulin has successfully engineered the absorption of glucose into the cells, blood glucose levels return to the healthy, baseline range within a few hours.
This touches on the function of insulin that's most familiar to the average person: its role in regulating blood glucose levels, also called blood sugar levels. Blood glucose or sugar serves as fuel for all the muscles, tissues, and organs of the body. Most importantly, it is the primary fuel for the brain. As such, it is extremely important that blood glucose levels be maintained within a very narrow range.
Low blood sugar, or hypoglycemia leaves us shaky, irritable, weak, and unable to focus or think clearly. Very high blood sugar levels wreak havoc on our organs and can even induce a coma. Insulin is released by the beta cells in the pancreas when blood sugar levels increase in response to ingestion of carbohydrates and other nutrients. When blood glucose levels are low, the secretion of insulin is inhibited.
Insulin is not only anabolic with regard to delivering fuel and building glucose stores. It also promotes muscle building and fat storage. Depending on your diet and exercise regimen, insulin can work to build muscle and improve body composition. Alternatively, if calories are consumed in excess, creating a positive energy balance, insulin works to clear excess circulating fatty acids in the blood by promoting their storage in adipose cells.
It's important to understand that the relationship between insulin and glucose goes both ways. When insulin levels in the blood are high, the liver's production and secretion of glucose decreases and systems throughout the body prioritize the growth and development of new cells. When levels are low, those effects are reversed, and widespread catabolism (the process by which cells are broken down to release the energy they contain) sets in. The catabolic effect associated with low insulin levels has a particularly prominent impact on stores of body fat.
When beta cells become damaged, insulin synthesis as well as insulin secretion become impaired. One example of this would be the autoimmune reaction that results in type 1 diabetes mellitus, the primary symptoms of which are abnormally high blood glucose concentrations as well as excessive catabolism through the body. Type 2 diabetes mellitus stems from the same cause—the destruction of beta cells—however, it's differentiated from type 1 diabetes in that damage is not spurred by an autoimmune reaction and is less severe.
A Timeline of Key Discoveries About Insulin
Because of the vital importance of insulin as a diabetes treatment, it has been intensely studied for close to a century.
In the early 1920s, a team of researchers from the University of Toronto hit on a method for extracting insulin from the pancreases of animals and purifying it to make it safe to administer to humans as a treatment for diabetes. This discovery earned them the Nobel Prize in 1923.
As an interesting side note, an eminent Romanian scientist named Nicolae Paulescu successfully extracted insulin and demonstrated its efficacy as a diabetes treatment prior to the Canadian team, however, his extract could not be used on humans. No mention of Paulescu's work was made when the Nobel Prize was awarded, which has since been viewed as a "historic wrong," in the words of Ian Murray, a professor of physiology, vice-president of the British Association of Diabetes, and founding member of the International Diabetes Foundation.
In 1955, biochemist Fred Sanger determined the order of the amino acids in insulin, making it the first protein to be sequenced. His work with insulin, which he found was made up of two chains of amino acids (the A chain containing 21 amino acids and the B chain 30) linked by disulphide bonds, led to the knowledge that all proteins found in the human body are composed of varying sequences of some or all of the same set of amino acids. This work resulted in another Nobel Prize, which was awarded to Sanger in 1959.
Insulin spurred another major scientific breakthrough in 1963 when it became the first protein to be chemically synthesized. However, it was not yet possible to produce it on a large scale, meaning that individuals with diabetes had to continue to use animal insulin, which causes side effects such as immune responses in some patients.
In 1969, Dorothy Hodgkin (also a Nobel Prize winner), used X-ray crystallography to map the molecular structure of insulin. This allowed researchers to learn more about the functions of insulin in the body as well as how it's produced.
The form of insulin used for diabetes care today dates back to 1978, when scientists used genetic modification to get bacteria to generate the A and B chains of insulin, then developed a chemical process to link the chains together. This allowed synthetic human insulin to be mass produced and diabetes to be treated far more effectively.
The 4 Different Types of Insulin
At this time, insulin therapy involves the use of four primary types of insulin differentiated by how rapidly the effect of insulin sets in, when the effect reaches its peak, and how long the effect lasts.
The four types are:
- Rapid-acting insulin
- Short-acting insulin
- Intermediate-acting insulin
- Long-acting insulin
Per information provided by the American Diabetes Association, the first type, rapid-acting insulin, can be detected in the bloodstream within 15 minutes of injection, reaches peak concentrations in the blood between 30 and 90 minutes, and continues to be detectable for approximately 5 hours.
Short-acting insulin can be detected within 30 minutes, reaches peak concentrations about 2 to 4 hours after injection, and remains present for between 4 and 8 hours.
Intermediate-acting insulin reaches the bloodstream between 2 and 6 hours after injection, peaks between 4 and 14 hours after, and stays in the blood for around 14 to 20 hours.
Long-acting insulin does not reach the bloodstream for 6 to 14 hours, reaches peak concentrations shortly after, and remains in the blood for between 20 hours and a full day.
Every diabetic has individual insulin needs and responses, and there's no single type that's universally best. Rather, it's important to tailor insulin therapy to a patient's specific needs. It's even possible to use two types mixed together to access a range of different delivery times, peaks, and durations.
Insulin's Role in the Development of Adverse Health Conditions
Experts have found that abnormal insulin levels as well as changes to the body's ability to detect the presence of insulin contribute to the development of several health conditions, including:
Diabetes mellitus: The symptoms of both type 1 diabetes and type 2 diabetes stem from insulin abnormalities resulting in hyperglycemia (high blood sugar levels).
- Type 1 diabetes is an autoimmune condition that causes the body to destroy the pancreatic beta cells that produce insulin, ultimately resulting in complete insulin deficiency.
- Type 2 diabetes results from either impaired insulin production, insulin resistance, or a combination of both. The mechanisms that cause type 2 diabetes have yet to be fully comprehended, but contributing factors seem to include a lack of physical activity and imbalanced diet.
- Metabolic syndrome: This accounts for a cluster of conditions including high blood pressure, high cholesterol and triglycerides, and abdominal obesity, all of which seem to originate from insulin resistance. Metabolic syndrome often precedes the development of type 2 diabetes as well as heart disease.
- Polycystic ovary syndrome (PCOS): This hormonal disorder affects women during their reproductive years, resulting in elevated levels of androgen and poorly functioning ovaries. It's common for PCOS to involve insulin resistance. Once insulin resistance sets in, the body increases its insulin production, which in turn leads to increased production of androgens.
- Cancer: Insulin promotes extremely rapid cell division, which can cause cancer to metastasize. High levels of insulin also appear to trigger dangerous changes to DNA regulatory genes that can result in cancer. Furthermore, tumors of the beta cells (whether cancerous or noncancerous) result in a condition called insulinoma that causes high levels of insulin as well as reactive hypoglycemia.
Let's get into some specifics about the role insulin plays in the development of these conditions.
Type 1 diabetes occurs because the beta cells of the pancreas stop producing insulin. The condition is either present from birth or from an early point in childhood. The treatment of type 1 diabetes necessitates careful monitoring of blood sugar levels in combination with regular insulin injections to keep those levels stable.
Type 2 diabetes, once called adult-onset diabetes, though it's now becoming quite common among adolescents and children, transpires when the body begins to require higher and higher levels of insulin in order for that protein to carry out its essential functions. This happens due to insulin resistance—though a sufficient amount of insulin is present in the bloodstream, the body cannot detect it, meaning it must continue to produce more and more and more. At a certain point, the demand for insulin exceeds the beta cell's ability to produce it, and synthetic human insulin must be introduced in order to regulate blood sugar levels.
As has been noted already, without enough insulin, physiological disturbances occur that result in unpleasant symptoms such as:
- Low energy levels
- Frequent infections
- Impaired eyesight
- Numbness or tingling in the extremities
- High levels of thirst
- Poor healing of cuts and bruises
As this transpires, the cells of the body shift away from glucose metabolism—since a reliable supply of glucose is no longer available—and begin the breakdown of fat stored as an emergency energy source. If the cells remain in this fat-fueled mode long enough, they begin producing ketones.
As a side note, individuals adhering to the keto diet intentionally pursue the production of ketones by strictly restricting carbohydrates in order to force the body to switch from glucogenesis to ketogenesis as its mode of energy production. In this resulting state of ketosis, the body burns off fat stores at a much higher rate than usual. Intentionally induced nutritional ketosis can be beneficial in terms of weight loss and other potentially positive physiological changes, however, diabetic ketoacidosis is not beneficial at all and is instead quite harmful. In addition to the question of intention, the two states can be differentiated by blood ketone levels. The blood ketone threshold for nutritional ketosis is 0.6 mmol/L. When those levels exceed 1.5 mmol/L, a person is at high risk of ketoacidosis. When left untreated, ketoacidosis can result in severe illness, coma, and even death.
Sometimes referred to as insulin resistance syndrome, metabolic syndrome involves the presence of at least three of the following five conditions:
- High blood pressure
- Low levels of high-density lipoprotein (HDL) cholesterol
- High triglyceride levels
- High fasting blood glucose levels
- Abdominal obesity
A growing consensus among experts holds that insulin resistance is the catalyst behind the development of metabolic syndrome. “Once acquired, those with a genetic predisposition would develop all the other aspects of the disorder,” they claim.
Other researchers believe insulin resistance arises from a sedentary lifestyle, but whether or not the insulin resistance comes first, it's clear that it plays a pivotal role in the pathogenesis of metabolic syndrome.
Polycystic Ovary Syndrome (PCOS)
Polycystic ovary syndrome results from imbalanced reproductive hormones. It can involve the presence of a fluid-filled cyst inside the ovaries, but the name is somewhat misleading as it's entirely possible for individuals to have PCOS without developing cysts.
It's also possible for PCOS to produce very little disruption to a person's life. In other cases, however, it leads to more serious health problems including type 2 diabetes and metabolic syndrome.
As touched on above, insulin resistance drives the development of PCOS. Some risk factors that lead to insulin resistance can't be controlled, but others relate to lifestyle such as diet and physical activity. Proactive steps can help prevent insulin resistance, and making adjustments can also help to reverse this condition.
Insulin has been implicated as a factor in overall cancer risk—specifically, high levels of circulating insulin appear to raise your odds of developing cancer.
Because insulin is a growth factor, hyperinsulinemia promotes extremely rapid cell division, which is not desirable when it comes to cancer cells. Cancer cells exposed to high insulin concentrations can proliferate and migrate aggressively.
DNA regulatory genes are also influenced by chronically elevated insulin and blood sugar, which can trigger changes or mutations in the cell. These alterations can lead to cancers in different tissues and organs in the body.
Last but not least, with insulinoma, the tumors (which can be noncancerous) constantly secrete insulin, thereby causing hypoglycemia (low blood sugar).
Understanding the Functions of Insulin in the Body
As touched on previously, the presence of glucose stimulates the body to secrete insulin. However, other macronutrients, hormones, and biological compounds also stimulate insulin secretion. The primary function of insulin, as well as its counterpart, glucagon, is to regulate blood glucose concentrations.
Basal Insulin Secretion
A very comprehensive article published in the Clinical Biochemist Reviews establishes the healthy basal level of insulin secretion when the body's in a fasting state as 0.25 to 1.5 units of insulin per hour. In healthy individuals, basal secretion maintains fasting insulin concentrations in the bloodstream of between 3 and 15 mlU/L. This allows for insulin-dependent entry of glucose into the cells of the body, prevents excessive breakdown of triglycerides, and minimizes glucogenesis, all of which ensures that blood sugar levels remain stable.
Glucose-Stimulated Insulin Secretion
When all is operating as it should, glucose-stimulated insulin secretion occurs in two distinct phases. The first phase is a rapid response, resulting in insulin secretion within 1 minute of glucose entering the bloodstream. This phase peaks in 3 to 5 minutes and only lasts for about 10 minutes.
The second phase has a slower onset. It's not apparent until 10 minutes after glucose reaches the bloodstream (at which point the first phase will be over, or close to over). The phase involves continuous secretion of insulin for the duration of the time that blood sugar levels remain elevated. The amount of insulin secreted is proportional to the concentration of glucose in the bloodstream.
The first phase involves insulin that has already been synthesized and stored, while the second phase requires the use of newly synthesized insulin.
The Release of Insulin in Response to a Meal
The neat and tidy insulin responses described above only occur in laboratory settings. In the real world, the secretion of insulin stimulated by food intake proves far more difficult to predict due to the multitude of variables involved, such as:
- Presence of specific nutrients, including amino acids
- Physical makeup of the foods
- Rate of gastric emptying
- Speed of gastrointestinal motility
Furthermore, neural input as well as other digestive hormones such as incretin affect insulin response.
Specific nutrients produce distinct insulin responses. For instance, non-esterified fatty acids (NEFA), which may come directly from high-fat foods or from the synthesis of excess carbohydrates, lead to increased output of glucose and reduce insulin sensitivity. There's some indication, too, that they alter glucose-stimulated insulin secretion—in the short-term, elevated levels of NEFA in the blood have been linked to increased glucose-stimulated insulin secretion, but chronically high levels of NEFA result in decreased glucose-stimulated insulin secretion as well as decreased insulin synthesis.
The Role of Insulin Receptors
First described by scientists in 1971, insulin receptors contain special proteins called insulin responsive substrates (IRS) that mediate the effects of insulin on the body's cells.
Four distinct IRS proteins have been identified and named (rather prosaically): IRS 1, IRS 2, IRS 3, and IRS 4.
IRS 1 controls most actions of insulin in the skeletal muscle cells. IRS 2 handles the liver as well as peripheral insulin signals and the development of pancreatic beta cells. The roles of IRS 3 and 4 remain somewhat more mysterious. IRS 3 can be found in fat cells as well as in beta cells and in the liver, while IRS 4 appear in the thymus, brain, and kidneys.
How Insulin Functions on a Cellular Level
The primary functions of insulin in the body's cells have to do with the metabolism of carbohydrates, fats, and amino acids from protein as well as the transcription and translation of mRNA.
- Carbohydrates: Insulin contributes to carbohydrate metabolism at many points during the process. It facilitates the diffusion of glucose from carbohydrates into fat and muscle cells, signals the presence of an abundance of intracellular energy, and more.
- Fats: Insulin instigates the synthesis of fatty acids in adipose tissue (fat) as well as in the liver and in the mammary glands during lactation. It also affects the metabolism of phospholipids.
- Protein: Insulin stimulates protein synthesis throughout the body. It also contributes to the transcription of mRNA as well as aiding translation of mRNA into ribosomal proteins.
In a big-picture sense, insulin's role has to do with the regulation of the body's cellular energy supply and the balance of micronutrients. When the body is in a fed, as opposed to fasting, state, insulin orchestrates the anabolic processes that lead to muscle growth (so long as a sufficient quantity of amino acids are available), tissue healing, and more. Insulin signals an abundance of energy, indicating to the body that it can halt the breakdown of fat stores and instead carry out fat synthesis.
How to Enhance Insulin Function
Aside from the nutritional strategy of minimizing large spikes in blood glucose, the most effective way to enhance insulin function is to stay physically active.
It makes sense that insulin is an important factor in making sure the body is properly fueled for physical activity. Insulin helps deliver glucose from the blood into the muscle cell. Once in the muscle, glucose is metabolized to produce energy to support physical exertion. Insulin also stores excess glucose as glycogen so that it can be used for energy at a later time.
Dietary protein and amino acids can also stimulate insulin release. Consuming a balance of carbohydrate and protein during exercise has been proven to stimulate more insulin than carbohydrate alone, resulting in faster delivery of glucose to working muscles.
Insulin is also needed to optimize recovery of muscles from a hard workout. Immediately after exercise, the muscle is primed to replenish fuel stores like glycogen and to rebuild and repair muscle proteins. During this period, insulin accelerates the rate at which glycogen and protein synthesis proceeds, up to 2 to 3 times the normal rate as long as carbohydrate and protein are ingested and made available.
Insulin likes to do these jobs, and can carry them out quite efficiently. However, for individuals who live sedentary lifestyles, the muscles use very little stored fuel, resulting in an abundance of excess fuels, carbohydrates, fats, and amino acids in circulation. The good news is, just a single bout of exercise can wake up the insulin receptors and enhance their sensitivity and functioning. This helps rebalance the body's energy utilization and storage processes.
In summary, insulin is an amazing hormone dedicated to ensuring that the food we eat is properly routed to where it is needed and when it is needed. A poor diet high in processed carbohydrates, excess energy intake, and lack of physical activity all tax the ability of insulin to do its job properly.
The overproduction of insulin, as it tries to overcome these challenges, has led to an interpretation that insulin in some way contributes to metabolic dysfunction and health complications. While it's true that abnormal insulin levels as well as changes to the body's ability to detect the presence of insulin can lead to the development of adverse health conditions such as diabetes, metabolic syndrome, polycystic ovary syndrome, and even cancer, insulin itself is not to blame.
Rather, the true instigating factors in the development of these conditions can be traced back to a person's genes, lifestyle choices, environment, or a combination of all the above. By supplying your body with a properly balanced diet and prioritizing physical activity as much as your other commitments and overall health allow, you can build a foundation for proper insulin function that will keep this crucial hormone operating as a "good guy, not a "bad" one.