If we are truly looking to maximize our health and metabolic function we need to master the crucial concept of balancing our blood sugar. In order to do that, we must understand how our organs, glands and hormones tightly regulate this process. Your blood sugar is deeply connected to a multitude of physiological processes that regulate the transportation and utilization of energy. Normal fasting glucose levels are usually in the range of 70 - 100 mg/dL. In the presence of health, the body should control blood sugar levels in a steady range. However, when complications are presented, drastic fluctuation will occur that can be highly problematic. Optimizing and controlling our blood sugar is not always as simple as it seems, and most individuals are simply addressing the symptoms of blood sugar fluctuations and not addressing the root issue.
HOW IS THE BLOOD SUGAR REGULATED?
As you consume a meal and digestion takes place, blood glucose (sugar) levels will naturally rise within the circulation. Carbohydrates and protein will elevate the blood glucose levels. In response to elevated blood glucose levels, your pancreas will secrete insulin (along with other hormones) to bring levels back down to baseline. Insulin will deliver glucose to various cells, such as, the muscles, fat, and other tissues in need of energy. Insulin will act to shuttle and transport glucose into the target cells of the body. Glucose is the cells primary source of energy, but the efficiency of that glucose utilization will be dependent of the presence of oxygen and T3. If glucose does not enter the cell properly and is elevated in the circulation it can become toxic to many organs including the kidney. Oppositely, in between meals and while sleeping the body will shift into a semi-fasted state, which will cause the blood sugar to go down. When levels drop the pancreas will respond by secreting glucagon (along with other hormones) to stimulate the liver to liberate glycogen for glucose production, which will be released into the circulation and delivered systemically to the cells in need of energy. This intricate balancing act of blood glucose going up after a meal, coming down during a fasted state, and being tightly regulated by the body's hormones is the essence of controlling your blood sugar.
A DEEPER LOOK AT WHAT’S INVOLVED
Most individuals stop after this basic information is established, but the real foundation for understanding is in the details. Therefore, it is necessary to look deeper at the primary organs and hormones that play the largest role in blood sugar regulation. Each organ that will be covered will pertain specifically to the concept of blood sugar. All of these systems tightly regulate blood sugar within the circulation (blood stream) and in the cell.
THE PANCREAS: HELLO HORMONES
As mentioned earlier, the pancreas is directly involved in how the body regulates the blood sugar. It is composed of two types of cells, exocrine and endocrine cells. The exocrine cells are responsible for secreting bicarbonate and digestive enzymes, and the endocrine cells are responsible for secreting several hormones. These hormones are the key determinants to whether levels will rise or fall in the circulation. The pancreas produces these crucial hormones through clusters of cells called the Islets of Langerhan. Within these clusters are three primary cell types; each responsible for secreting specific hormones that affect levels differently.
Glucagon: When the blood sugar goes down glucagon will be secreted and will signal the liver to liberate glycogen to produce glucose. Depending on glycogen levels (and other factors), glucagon will also elevate glucose levels by converting amino acids and other by-products into glucose, and dietary fats into ketones for energy. This hormone is responsible for preventing hypoglycemia (low blood sugar). Glucagon is catabolic and lipolytic in nature and will liberate storage forms of glucose, amino acids, and fatty acids. Glucagon is considered to be the antagonist to insulin.
In other words: Glucagon is responsible for the release of stored energy. Glucagon stimulates glycogenolysis, gluconeogenesis, ketogenesis, proteolysis, and lipolysis.
Insulin: When blood glucose levels are elevated in the circulation insulin will be secreted to bring levels down. Insulin does this by transporting glucose from the circulation into major target cells such as the muscle, fat and red blood cells. Along with glucose, Insulin will drive amino acid uptake and protein synthesis. Insulin is known as an anabolic hormone, or tissue building hormone. Thus, it is also a storage hormone; storing additional glucose into glycogen, and excess glucose and amino acids into triacylglycerols and into fat, and excess fatty acids into fat.
In other words: Insulin is responsible for transporting and storing energy. Insulin stimulates glycogenesis, protein synthesis, and lipid synthesis.
Amylin: Amylin is secreted along with insulin and assists in lowering the blood sugar levels when they are elevated. This peptide hormone also slows down gastric (stomach) emptying, thus slowing down blood glucose spikes. This hormone also triggers satiety, which makes you feel full.
Somatostatin: This hormone regulates the action of the alpha and beta cells. Somatostatin acts as an inhibitory hormone, capable of suppressing the release of insulin and glucagon.
THE LIVER: I GUESS YOU ARE IMPORTANT
The liver must not be overlooked when considering the regulation of blood sugar. This organ is the primary site for macronutrient metabolism, which in turn acts like a control center for blood sugar management. It converts glucose into glycogen and produces glucose from glycogen and other by-products, which is the basis for blood sugar regulation. Many of the hormones related to blood sugar act on and are metabolized by the liver. The liver is intricately involved with the pancreas and if it is functioning less than optimal the pancreas will suffer and can become overloaded.
The liver functions like an energy reservoir, and will control glucose production and storage depending on the body’s energy requirements. The primary substance for this control is glycogen, which is a storage form of glucose. Liver glycogen is the body’s go to for restoring blood sugar levels during the semi-fasted state, supporting the system for a several hours to a day (depending on levels). During this state, or anytime the body requires glucose, glucagon will stimulate the liver to tap into the glycogen reserves and break it down into glucose. This breakdown of glycogen for needed energy is called glycogenolysis.
After a meal or when glucose levels are elevated, insulin will signal the liver to store additional glucose in the form of glycogen, which serves as a semi-immediate energy reserve for later times. This formation of glycogen from additional glucose is called glycogenoesis. Thus, liver glycogen is vital for maintaining an energy balance without utilizing non-glucose substances for energy. The consumption and metabolism of fructose is crucial for replenishing liver glycogen reserves and therefore liver health.
During a fasted state and in the absence of glycogen, the liver will transition into the metabolic process of gluconeogenesis, which is when the body must convert non-glucose by-products into glucose or ketones. The body will break down and convert amino acids, lactic acid, and other by-products into glucose, and fatty acids into ketones for energy. However, this is a more costly process and will require the activation of the sympathetic nervous system. Gluconeogenesis is predominantly stimulated by glucocorticoids and will set off the stress response.
THE ADRENALS & THE STRESS RESPONSE
When our physiology shifts into a stress state our blood sugar will rise to meet the energy demands of the survival situation that is being interpreted. Unfortunately, many of the stressors in today's lifestyle stimulates this response even when we do not need additional glucose for energy. Furthermore, blood sugar fluctuations, especially low blood sugar (hypoglycemia), place another major stressor onto the system. Regardless of the type of stress(es), the sympathetic nervous system will be stimulated, which will signal the adrenal glands to secrete hydrocortisone (cortisol), cortisone, epinephrine (adrenaline) and nor-epinephrine. Cortisol and adrenaline are the major contributors in raising the blood sugar, and are released to produce glucose from the liver and other tissues, thus elevating circulatory levels of glucose.
EPINEPHRINE (ADRENALINE): Epinephrine is classified as a catecholamine, which is a hormone and a neurotransmitter, and is secreted from the core of the adrenal gland known as the medulla. It liberates glucose from glycogen in the liver and peripheral tissue through glycogenolysis and gluconeogenesis. Epinephrine also increases glucose levels indirectly by stimulating glucagon and adrenocorticotropic hormone (ACTH), which stimulates cortisol. This contribution to increasing ACTH and thus cortisol, indirectly implies that epinephrine in excess can inhibit insulin sensitivity.
CORTISOL: This hormone is a glucocorticoid, named for one of it’s primary functions, which is to increase glucose levels when the body is in immediate need. This is a survival mechanism for when the blood sugar gets too low (a hypoglycemic state). In this state cortisol will be released from the cortex of the adrenal glands, and will convert non-glucose by-products into glucose through gluconeogenesis. However, this process occurs at the expense of breaking down tissue in the body such as muscle, thymus and skin tissue. Excessive cortisol also suppresses the uptake of glucose into the muscle and fat cells.
Excessive adrenaline, cortisol and overall stress can cause insulin resistance and lead to metabolic complications.
The stress response intensity is highly dependent on liver glycogen levels for proper stabilization. If liver glycogen is depleted and energy levels are in demand; the body will rely heavily on these two hormones, especially cortisol, to stimulate gluconeogenesis. This metabolic pathway results in tissue wasting, and excessive production will increase insulin resistance. The constant utilization and reliance on gluconeogenesis can result in a constant alarm response and lead to complications. The health of the liver, proper glycogen replenishment, and controlling stress levels is imperative for handling the blood sugar. Without controlling our stress response our blood sugar levels can be all over the map, not to mention it can also interfere with other physiological systems such as the thyroid.
Both epinephrine and cortisol stimulates hormone sensitive lipase (HSL), which is an enzyme that liberates fat from adipose (fat) tissue. This releases free fatty acids and glycerol, which contributes to the utilization of gluconeogenesis to produce energy. However, fat liberation can release excessive amounts of stored polyunsaturated fats, estrogen and other pro-inflammatory by-products, which could be damaging to several systems. Proper nutrition should always be implemented to support the proper detoxification necessary for fat liberation, increased metabolic rate and body fat loss.
THE SMALL INTESTINE: MORE HORMONES
The small intestine is the site for lots of action, including digestion and absorption, but we will only analyze the endocrine functions and just look at the hormones of relevance. The two hormones of importance are peptide hormones known as incretins, which are gastrointestinal secreted hormones that decreases blood glucose levels. These are secreted by various sections of the small intestinal lumen in response to glucose in the circulation.
GLP-1 (Glucagon-Like Peptide 1) GLP-1 contributes by stimulating the beta cells of the pancreas to secrete insulin while suppressing the alpha cells from secreting glucagon. This hormone works synergistically with insulin to decrease the blood sugar. GLP-1 brings levels down immediately after a blood sugar spike, but has a relatively short half-life, which helps control potential hypoglycemia several hours after. GLP-1 works similarly to amylin, by slowing down the rate of gastric emptying and controlling appetite by signaling the brain that the system is full.
GIP (Glucose-dependent Insulinotropic Polypeptide) GIP functions in the same way as GLP-1, stimulating the pancreas to produce insulin and inhibits glucagon. The stimulation of GIP is triggered by high levels of glucose in the small intestine, hence the name glucose-dependent. GIP is also correlated with fat storing enzymes and lipid metabolism.
WHAT NUTRIENTS AFFECT THE BLOOD SUGAR?
This is a question in which the answer should be more widely known. Based off the topic and the question, most minds will jump to the obvious nutrient of carbohydrates. Yes, carbohydrates do increase the blood sugar levels, for healthy digestion will break down carbohydrates into simple sugars. However, not all carbohydrates are metabolized the same, and not all affect the blood sugar levels that same. In general, glucose is the main monosaccharide (simple sugar) that contributes to elevated levels, and starch is composed of multiple glucose units. Therefore, starch products such as wheat, potatoes, rice, etc., will certainly elevate blood sugar levels. When it comes to the digestion of starches and grains, the processing, viscosity, fiber, type, and more will affect the degree of the blood sugar response. Now, sugar or sucrose (glucose + fructose) impacts the blood sugar differently. Fructose will slow down the process because there is a concentration gradient during absorption, which slows the transportation process. Thus, the consumption of fruits, honey, syrups and others will have less impact on blood sugar.
When consuming protein the body’s blood sugar will also rise, and in if not balanced with other macronutrients, will cause a dramatic increase. Last but not least, fat is the one nutrient that actually slows down the digestive process and minimizes blood sugar spikes. The rate at which the stomach empties fat into the intestines is naturally slower and requires more time. Simply incorporating fat into a meal can dramatically decrease the blood sugar and insulin spike. So you ask, why aren’t more people utilizing fat consumption to regulate blood sugar? That’s another great question.
As illustrated above, our blood sugar levels are influenced by multiple physiological systems. The health of each organ and the hormones related, will dictate our capacity to optimize energy utilization. It’s important to understand that if issues arise they are dependent on the individual's current health, nutritional habits, lifestyle factors, and more. Highlighted below are some of the most common problems related to the concept of blood sugar.
HYPOGLYCEMIA: A condition in which blood glucose levels go too low and result in a myriad of symptoms. The primary concern is generally a lack of glucose to the brain, which can cause major dysfunctions neurologically. When levels get into the low, below 70 mg/dL (completely dependent on the individual) hypoglycemia is usually presented, and glucose is needed to bring levels up. Now, if insulin levels are high or not controlled (elevated for extended periods) then glucose levels will commonly fall below the norm, setting off this cascade.
REACTIVE HYPOGLYCEMIA: A pattern or consistent occurrence of hypoglycemia within several hours after eating a high carbohydrate meal. Again excessive insulin or prolonged insulin release will drive level down. There is no diagnosis of diabetes while individuals are going through this.
HYPERGLYCEMIA: Excessively high levels of blood glucose in the circulation. The presence of glucose and insulin in high levels in the circulation are toxic and dangerous. The glucose will connect with proteins in the circulation, creating glycation reactions and cross-linking. This will slow down the circulation and decrease optimal blood and cellular flow. Excessive cross-linking will lead to Advance Glycation End-Products (AGEs), which lead to a whole host of problems.
DYSGLYCEMIA: Abnormal blood glucose levels or fluctuations of hyperglycemia and hypoglycemia.
HYPERINSULINEMIA: Excessive insulin levels in the blood circulation in relationship to glucose. This condition is generally seen in individuals that have cellular / receptor problems, usually present during insulin resistance. The pancreas and its beta cells are still performing or even over performing, but the connection at the cell level is disrupted. Insulin is a storage hormone and excessively high levels lead to lipid complications, dyslipidemia, obesity, and metabolic syndrome (which is a collection of symptoms). Insulin will also create several other complications such as: mineral imbalances that can lead to hypertension, increased levels of aromatase that converts testosterone to estrogen, and other far reaching issues.
INSULIN RESISTANCE: Insulin receptors located on target cells become defective, leading to an inability to uptake glucose. This condition is a major factor in most if not all of these problems highlighted. This complication can develop from any number of issues, from insulin overload to excessive cortisol.
DIABETES: A metabolic illness related to the above problems and diagnosed by hyperglycemic conditions. From a medical perspective, a fasting glucose level of 126 mg/dL and above, or an oral glucose tolerance level of 200 mg/dL and above, is considered diabetic. Diabetes can present any of the symptoms above. It is also related to neuropathy, nephropathy, increased risk of cardiovascular problems, increased infection, and more.
With this foundation set, we can explore the root causes and real solutions to these troubling issues.
Pottenger, F.M. (1919). Symptoms of visceral disease: a study of the vegetative nervous system
in its relationship to clinical medicine. St. Louis, MO: Mosby Company / Forgotten
Widmaier, E. P., Hershel, R., Strang, K. T. (2008). Vander’s Human Physiology: The
Mechanishms of the Body Function (11th Ed.). New York, NY: McGraw Hill