By Catherine M. Haug, Moved from Syndrome-X article February 2007; moved and updated April 2021.
Insulin is well known as the pancreatic hormone that regulates blood sugar, as well as other less-known responsibilities that are discussed in this article. Perhaps one of the most troubling issues concerning insulin, is when brain cells can no longer take-up needed insulin, which is believed to be the cause of Alzheimer’s disease. Another is its role in determining lifespan.
- Includes: 1. Insulin: The Master Regulator; 2. Alzheimers & Brain Insulin; 3. Lifespan Control; 4. Insulin Control of Sugar Uptake by Cells; 5. Effect of Cortisol on Sugar Uptake
- See also (this site): 1. Diet and Health Menu*; 2. Notes on Insulin Resistance (IR); 3. Choline, Inositol, and Insulin Resistance; 4. Ketogenic Diet; 5. Cyclical Ketogenic Diet (CKD) and Metabolic Mitochondrial Therapy (MMT)
Insulin: The Master Regulator
While insulin is well known as the pancreatic hormone that regulates blood sugar, it has many more responsibilities as well. Its overall responsibility is to control the rate of aging (lifespan). (2) A person’s lifespan is determined by a delicate balance between anabolic (building up) and catabolic (tearing down) processes in the body, and insulin has a part to play in regulation of both sides of the balance.
Studies of centenarians (people who live over 100 years) reveal there is little they have in common; for example, some never smoke while others are life-long smokers. Yet there are three things — three metabolic indicators — that are relatively consistent among centenarians:
- low serum glucose;
- low serum triglycerides;
- low serum insulin.
The common denominator for all three of these indicators is insulin. Cells of centenarians are consistently sensitive to insulin; insulin sensitivity is one of the most important markers of lifespan. (6)
Check out this interesting and informative website regarding the actions of insulin and glucagon* from the University of Manchester (England) on Hormonal Control of Metabolism (13). [Cat’s note: that particular link is no longer valid as of April 2021; however, I included two other links that discuss the same topic, for reference 13.]
‘* What is glucagon (10b)?
“Glucagon is a hormone that works with other hormones and bodily functions to control glucose levels in the blood. It comes from alpha cells found in the pancreas and is closely related to insulin-secreting beta cells, making it a crucial component that keeps the body’s blood glucose levels stable.”
Alzheimers and Brain Insulin
Recent research has also developed a link between insulin and Alzheimers.
- A 2004 study found that people with diabetes have a higher risk of developing Alzheimers, the disease that cases memory loss and dementia.
- A 2005 study reported that the pancreas is not the only organ that produces insulin; this hormone, believed to be essential for the survival of nerve cells, is also produced in the brain. A drop in brain insulin production contributes to degeneration of brain cells. (11)
- And in 2007, researchers at Northwestern University reported that a specific toxic protein known as ADDL removes insulin receptors from brain cells, so they become insulin resistant and cannot respond to brain insulin. This ADDL protein is found in all Alzheimers patients, and is being investigated as an early test to detect the beginnings of the disease. (11, 12)
Lifespan Control
How does insulin control the rate of aging? By regulating:
- Sugar and fat metabolism. Insulin:
- Initiates the cellular processes that move glucose into cells for energy production;
- Causes any excess sugar to be stored in adipose (fat) cells as fat;
- Suppresses glucagon and growth hormones, which regulate the burning of fat, stored fat, and rate of muscle development, respectively.
- Excess insulin in the blood promotes fat (from excess dietary carbs and sugars), and then wards off the body’s ability to lose that fat, both of which can shorten the lifespan of the individual. (7)
- Other hormones, either directly or indirectly:
- Thyroid hormones: Insulin regulates the conversion of thyroid hormone T4 (the stored version) to T3 (an active version) in thyroid cells and the liver. (2a) Thyroid hormones regulate cellular protein, fat and carbohydrate metabolism, thus affecting HOW the cell uses these energetic compounds. In this way, they can increase basal metabolic rate, affect protein synthesis, and increase the body’s sensitivity to other hormones like adrenaline. (3a)
- Growth hormone: Insulin regulates IGFs (Insulin-like Growth Factors) by regulating growth hormone; (2a) IGFs are polypeptides with similar structure to insulin, that bind to unique IGF receptors (as well as insulin receptors), to regulate certain functions within the cell: IGF-I regulates cell growth and development, especially nerve cells, and cellular DNA synthesis; IGF-II is essential for development and function of organs, such as brain, liver and kidney. (3c)
- Glucagon: Insulin and glucagon have opposite (antagonistic) effects on blood sugar: Insulin secretion increases as blood sugar increases above the level of homeostasis (balance), and then works to move the sugar from the blood to the cells. Glucagon secretion increases as blood sugar decreases below the level of homeostasis, then works to break down stored fat into glucose. Both insulin and glucagon are secreted initially after ingestion of food, but as insulin levels rise in response to rising glucose, glucagon secretion is actively suppressed until sugar levels normalize. (10a,10b)
- Sex hormones: Insulin regulates creation of sex hormones (DHEA, andosterone, testosterone, progesterone, estrogen) from cholesterol. Insulin also regulates levels of sex-hormone-binding globulin, a protein used to transport sex hormones through the blood to the cells. (2a)
- Entry of amino acids into cells as part of it’s overall control of anabolic processes (processes that ‘build up’ body tissues, such as protein synthesis); (8)
- Level of certain ions & minerals in the blood:
- Calcium (2a)
- Chromium (5, 6)
- Magnesium (1)
- Phosphate (8)
- Potassium (8)
- Sodium (1)
- Zinc (6)
Insulin Control of Sugar Uptake by Cells
Under normal circumstances, when the brain detects an excess of sugar (glucose) in the blood (such as after a meal): (8)
- The brain sends a messenger to the pancreas to manufacture and release insulin into the blood stream.
- Insulin then travels to a desired cell where the sugar can be burned for energy, or be stored (as glycogen) if not needed for energy.
- Glucose in the blood cannot travel across the cell membrane without help, so the insulin binds to an insulin receptor embedded in the cell membrane, and then sends a signal (via protein messengers) for assistance, a ‘taxi.’ That is, the insulin initiates the glucose-uptake process.
- The protein taxi, called a GLUT-4 transporter in muscle cells, travels to the surface of the cell (the membrane), “grabs” the glucose molecule and retreats with its passenger back into the interior of the cell.
- When the energy burning cells have enough sugar, a series of enzyme-controlled steps cause the activity of the insulin receptors to be turned to “off.” (Conversely, when the cells desire more sugar, the receptors are turned to “on.”)
- If there is still an excess of glucose in the blood, insulin continues to be secreted. This insulin cannot bind to receptors that are “off,” so it searches for receptors that are “on.” These are likely found in the liver.
- The liver cells take up the excess sugar in a process similar to that for muscle cells, but utilizing a different GLUT transporter, and convert the sugar to triglycerides, with fatty acid chains comprised mainly of palmitic acid (a saturated fatty acid).
- These triglycerides are then packaged into Very Low-Density Lipoproteins (VLDL) for transport in the blood to the adipose cells, which store the triglycerides.
[Refer to Physiologic Effects of Insulin (8) for an excellent detailed description of this process, including a wonderful animation that illustrates better than words, how this happens.]
Effect of Cortisol on Sugar Uptake
Cortisol, an adrenal glucocorticoid hormone, has the opposite effect of insulin, brought on by the stress response, to make glucose available to muscle cells. While insulin seeks to lower serum glucose by pushing it into the cells, cortisol seeks to raise serum glucose by inhibiting cellular uptake and stimulating processes in the liver to convert amino acids and fatty acids to glucose. (3b)
Cortisol inhibits cellular uptake by limiting the movement of glucose transporters to the cell surface (step 4 of glucose uptake described above), making the cells less sensitive to the effect of insulin, i.e., making them insulin resistant until cortisol levels retreat as result of a negative feedback mechanism. (7)
References and Sources:
- yourhealthbase.com/diabetes.htm (link not secure)
- Mercola:
- Wikipedia:
- (moved to 3b)
- power-surge.com/educate/holt_diabetes_syndromex.htm (link no longer valid, Apr 2021)
- westonaprice.org/moderndiseases/diabetes.html (link no longer valid, Apr 2021); try:
- usyd.edu.au/su/rirdc/projects/study17.html no longer works; try:
- arbl.cvmbs.colostate.edu/hbooks/pathphys/endocrine/pancreas/insulin_phys.html (no longer works); try:
- not used (moved to (3c)
- cal.man.ac.uk/student_projects/2000/mnby7lc2/factors_affecting_secretion.htm (no longer valid); try:
- articles.mercola.com/sites/articles/archive/2007/10/16/is-alzheimer-s-a-form-of-diabetes.aspx < no longer valid; see references (2a, 2b) above
- Original link (https://faseb.onlinelibrary.wiley.com/journal/15306860 does not pull up the intended article; it replaced an earlier link;* try the following:
- elp.manchester.ac.uk/pub_projects/2000/mnby7lc2/METABOLISM.HTM#actionstable1 is no longer valid; try:
‘* re: ref 12: the original link that no longer works was: fasebj.org/cgi/content/abstract/fj.06-7703comv1?maxtoshow=&HITS=10&hits=10&RESULTFORMAT=&author1=William+L.+Klein&andorexactfulltext=and&searchid=1&FIRSTINDEX=0&sortspec=relevance&resourcetype=HWCIT
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