Insulin and blood sugar regulation

The human body is fantastically complex. Numerous body parts, organs, structures and even individual cells coordinate with each other to keep us alive. Each system strives to maintain an optimal range (i.e., homeostasis) despite varying internal and external signals. Blood sugar (i.e., glucose) regulation is an example of the constant exquisite coordination that produces everything from basic physiologic functions to elite athletic performance.

Every cell in the human body can use glucose as a direct fuel source to generate adenosine triphosphate (ATP), a high-energy molecule that, for example, powers muscle contractions. The major consumers of glucose are the brain and liver as well as muscle and adipose tissue (fat cells). The brain, for example, uses 120 g of glucose every day, accounting for approximately 60 percent of the usage by the whole body when at rest (1).

Some cells convert glucose into other energy forms, such as:

Glycogen (many glucose molecules linked together), which is primarily made and stored in the liver and muscles.

Fatty acids and ketone bodies. Both can be made in the liver. The adipose tissue makes fatty acids. Ketone bodies are released directly into the blood. Fatty acids, as lipids, can either be stored where they are made or released into the blood.

The protein hormone insulin regulates glucose homeostasis. Insulin is secreted from the beta cells of the pancreas into the blood in response to elevated blood glucose levels. The release generally results from eating and is most responsive to the ingestion of carbohydrate. For example, a meal composed only of carbohydrate can increase insulin levels from a low baseline to levels 10 times higher; a meal that is composed of only fat and protein might cause up to a twofold or threefold increase (2). When the increased insulin is detected by insulin receptors on the surface of cells, it signals those cells to absorb glucose from the blood. As a result, the internal cell concentration of glucose is increased, and the glucose concentration in the blood is reduced. Within the cells, various responses can take place such as:

Increased glycogen synthesis.

Increased fatty acid synthesis.

Increased protein synthesis.

Increased cellular growth.

Up-regulated glycolysis (the process of burning glucose anaerobically to make ATP).

Decreased net breakdown of proteins, fatty acids and glycogen.

Insulin is one of the most powerful central regulators of metabolism. Its presence is a signal of energy sufficiency that drives energy storage (e.g., as glycogen or fatty acids) or begins energy-consuming processes such as cell division. The liver, adipose tissue and skeletal muscle are the predominant targets of insulin action (3). Bulk glucose uptake by the brain happens without insulin, although research suggests insulin affects the brain’s control of energy and glucose homeostasis (4,5).

When insulin is low (e.g., several hours without food), the opposite responses take place, such as the breakdown of glycogen and fatty acids. Other hormones—such as glucagon, somatostatin, cortisol, growth hormone and adrenaline—might inhibit insulin’s effects in various conditions. Insulin can therefore be considered a comprehensive fuel-selector switch: Its presence shifts the body toward carbohydrate use, and its absence shifts the body toward fat use.

Daily Examples of Control

A full night of sleep is essentially a 10-12-hour fast. When you wake up, blood glucose levels are lower than the day’s average; the normal range is approximately 70 to 100 mg/dL. Within the first hour after eating a meal, blood glucose can spike to greater than 160 mg/dL. With the action of insulin, levels should drop to below 140 mg/dL two hours after a meal, indicating the individual is insulin “sensitive”; i.e., he or she responds to normal rises and falls of insulin. This is a cycle that repeats itself every day. An inability to lower blood glucose in a timely fashion after a meal is indicative of problems regulating glucose homeostasis (see below).

During exercise, muscles initially utilize the existing supply of ATP and phosphocreatine, which are the fuel for the high-power-output, short-duration phosphagen pathway. This immediate source of energy lasts for approximately 10 seconds. As ATP within muscles is depleted, the fuel source shifts to free glucose (primary) and glycogen (secondary), which are processed utilizing the glycolytic pathway. Skeletal muscle contains the largest store of glycogen—approximately 500 g. The glycolytic pathway, when tested under maximum effort, dominates energy production for approximately two minutes. Glycolysis can contribute to energy beyond this duration; however, it is particularly dependent on the individual’s intensity and genetics. Longer duration activities utilize fats as the predominant fuel source.

Blood glucose levels often rise during exercise (6); the liver is responsible for this increase. While the liver can break down its stores of glycogen (approximately 100 g) or create glucose from other sources (gluconeogenesis) and release it into the blood, muscle cells cannot release glucose into the circulation. This elevated blood glucose results in an insulin release that further aids the influx of glucose into the muscle cells that need it (6). Exercise also triggers muscle cells to take up blood glucose by a mechanism that does not require insulin—an important way of maintaining glucose homeostasis. Exercise can increase one’s insulin sensitivity via this mechanism because insulin can remain low despite the increase in blood sugar. During post-exercise recovery, blood glucose levels fall back to normal as muscle cells replenish glycogen stores to pre-exercise levels

Type 1 and Type 2 Diabetes

Type 1 diabetes occurs from an autoimmune process that destroys the beta cells of the pancreas. Without these cells, little or no insulin is produced. In the absence of insulin, blood glucose would remain dangerously elevated. Injections of insulin to normalize blood glucose are necessary to live with this condition.

Conversely, Type 2 diabetes begins with elevated blood glucose with the presence of insulin resistance. When insulin resistant, muscles, the liver and/or adipose tissue, etc. no longer respond to the normal level of released hormone. This lack of response prevents the cells from absorbing glucose from the blood, keeping levels higher than normal baseline levels. In addition, when the liver becomes insulin resistant (i.e., interpreted as a signal that blood glucose is low), it responds by breaking down glycogen and releasing even more glucose into the blood, requiring even more insulin to be released. Over time, the amount of insulin that needs to be released for tissues to absorb blood glucose rises (i.e. hyperinsulinemia). As Type 2 diabetes progresses, the beta cells of the pancreas might not be able to produce the quantity of insulin needed to properly control blood glucose. In some cases the beta cells cease to function and little or no insulin is released, creating at a state similar to Type 1 diabetes. Genetic, as well as environmental factors (such as diet, sedentary behavior, inflammatory state and even resident intestinal bacteria), can increase the risk of developing Type 2 diabetes (7).

Hyperglycemia and Hyperinsulinemia

Acute problems occur with low blood glucose (hypoglycemia), defined as lower than 70 mg/dL. Due to the amount of glucose used by the brain, symptoms can include dizziness, lack of coordination and disorientation when blood glucose is low (8). Chronically elevated blood glucose (hyperglycemia), greater than 126 mg/dL after an eight-hour fast, can pose long-term health risks, including Type 2 diabetes (9).

The constant elevation of blood glucose can result in an increased amount of insulin in the blood. Two overarching biologic processes control the amount of circulating insulin: the amount secreted from the pancreas and the rate of its clearance from the blood (10). Increased secretion, decreased clearance or both can lead to hyperinsulinemia. In this condition, the normally exquisite metabolic control insulin provides is deranged. Hyperinsulinemia is a common element involved in the risk factors for metabolic syndrome: hypertension, obesity, dyslipidemia and insulin resistance (11). Problems ensue because elevated insulin can continuously signal the liver to take up glucose and make glycogen as well as fatty acids, causing a net gain of liver fat and increasing the risk for fatty liver disease (12). Alternatively, if the liver becomes insulin resistant from the constant elevated levels of the hormone (interpreted as low blood glucose), it responds by initially releasing glucose until its glycogen stores are depleted and then shifts to releasing triglycerides and LDL particles into the blood (11). While these lipids can provide energy, the elevated levels also pose a long-term atherosclerotic and stroke risk. Hyperinsulinemia can occur in lean as well as obese individuals.

Obesity is not indicative of insulin resistance or hyperglycemia. Some insulin-sensitive (i.e., normal glucose regulation) obese individuals appear to have protective traits (higher aerobic fitness, lower inflammation, lower liver fat and smaller fat cells) compared to insulin-resistant obese individuals, indicating there is more to the pathology of obesity than mere weight gain (13). The insulin-sensitive obese appear to maintain glucose control with a physiologic and genetic capacity for large fat stores.

Obesity is the result of excessive caloric consumption relative to the body’s needs. However, understanding the complex role insulin plays in metabolism reveals deficiencies in the resulting simplistic explanation that fewer calories always equate to weight loss. Author Gary Taubes stated, “Imagine we were talking about the problem of poverty, and I said the cause is that people make too little money and spend too much. Would I have told you anything meaningful or given you any understanding of the societal forces that cause people to be poor?” (14).

Diets high in refined carbohydrates result in a constant elevated level of insulin and can lead to fat deposition (in the liver and adipose tissue), elevated blood lipids, lowered desire to be physically active and increased appetite (15). These elements create a vicious cycle. The types of food ingested, the frequent (or constant) glucose dysregulation and the subsequent biochemistry drive behaviors that lead to a positive energy balance, not the reverse (15). Yes, calories matter in the end, but the composition of those calories determines their physiologic/metabolic effects.

The CrossFit prescription of constantly varied functional movements at high intensity, combined with meat and vegetables, nuts and seeds, some fruit, little starch and no sugar, provides a remarkably elegant solution for maintaining glucose regulation and body weight, as well as for avoiding hyperinsulinemia.


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Marliss EB, Vranic M. Intense exercise has unique effects on both insulin release and its roles in glucoregulation: Implications for diabetes. Diabetes 51 (Suppl 1:S271-83), 2002. Available here.

Filippi BM, Mighiu PI, Lam TK. Is insulin action in the brain clinically relevant? Diabetes 61(4): 773-5, 2012. Available here.

Gray SM, Meijer RI, Barrett EJ. Insulin regulates brain function, but how does it get there? Diabetes 63(12): 3992-7, 2014. Available here.

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National Institute of Diabetes and Digestive and Kidney Diseases. Low blood glucose (hypoglycemia). Available here.

Yan LJ. Pathogenesis of chronic hyperglycemia: From reductive stress to oxidative stress. Journal of Diabetes Research Article ID 137919: 2014. Available here.

Kim MK, Reaven GM, Kim SH. Dissecting the relationship between obesity and hyperinsulinemia: Role of insulin secretion and insulin clearance. Obesity 25(2): 378-383, 2017. Available here.

Roberts CK, Hevener AL, Barnard RJ. Metabolic syndrome and insulin resistance: Underlying causes and modification by exercise training. Comprehensive Physiology 3(1): 1-58, 2013. Available here.

Pearson T, Wattis JA, King JR, MacDonald IA, Mazzatti DJ. The effects of insulin resistance on individual tissues: An application of a mathematical model of metabolism in humans. Bulletin of Mathematical Biology 78(6): 1189-217, 2016. Available here.

Samocha-Bonet D, Chisholm DJ, Tonks K, Campbell LV, Greenfield JR. Insulin-sensitive obesity in humans—a 'favorable fat' phenotype? Trends in Endocrinology & Metabolism 23(3): 116-24, 2012. Available here.

Wency Leung. Gary Taubes on his new book and why he won’t eat Christmas sweets. The Globe and Mail: Dec. 23, 2016. Available here.

Wells JC, Siervo M. Obesity and energy balance: Is the tail wagging the dog? European Journal of Clinical Nutrition 65(11): 1173-89, 2011. Available here.

All URLs accessed Feb. 9, 2017.

About the Authors

Jon Gary received his doctorate in molecular biology from UCLA. He is a Certified CrossFit Level 3 (CF-L3) Trainer and Flowmaster for the CrossFit Specialty Course: Kids. He has been doing CrossFit since 2003. He lives in San Diego, California, with his wife and coaches teenagers at CrossFit Escudo.

E.C. Synkowski, Certified CrossFit Level 4 Coach (CF-L4), is a Flowmaster for CrossFit Inc. Seminar Staff and has worked at more than 200 seminars. She is the Program Manager for the Training Department and is pursuing a master’s degree in human nutrition and functional medicine (anticipated completion in 2017).

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