Insulin resistance is the linchpin of many diseases of modern life like metabolic syndrome, obesity, and Type 2 diabetes. Knowing about how insulin resistance develops provides a better understanding of the familiar and deadly diseases that may be affecting you or someone you know.
Normal Glucose Metabolism
All the cells in the body need a constant supply of fuel to run. The primary fuel is glucose.
Whenever we eat, the carbohydrates are broken down into simple sugars like glucose. That glucose can either be used right away or stored for future use. Insulin is the primary hormone that stores glucose in the skeletal muscles and the liver. The skeletal muscles need glycogen for muscle contraction to produce movement. The liver serves as a storage buffer to replenish the circulating blood glucose for other organs like the brain and the rest of the body. If the demand for glucose is high and the liver’s glycogen stores get low, then it turns on its own glucose factory. This assures a steady source of fuel for body functions.
Development of Insulin Resistance
If there is no exercise, then the glycogen stores in the liver and muscles do not get used up. This makes the liver and skeletal muscles “resist” the effect of insulin to store more. That condition is called insulin resistance (IR). Add to that a habitual high carbohydrate and high-fat diet, and you end up with excessive levels of circulating glucose (hyperglycemia) and lipids in the blood.
The body does not like hyperglycemia, and to counter the resistance, the pancreas produces more insulin to get that glucose lower. The high insulin level is called hyperinsulinemia, HI.
The muscles and liver respond to the HI by storing extra glucose. But since both can only add so much glucose, they become insulin resistance again. In response to the higher insulin resistance, the pancreas produces more insulin that leads to more HI. If the sedentary and high caloric lifestyle continues, then a vicious cycle of IR promoting more HI that leads to more IR and so on and so forth ensues.
The High Price of Insulin Resistance and Hyperinsulinemia
Fatty Liver
IR in the liver makes the liver turn the extra glucose into fat thru a process called de-novo lipogenesis and makes fat out of glucose. The excess fat gets stored in the liver producing a fatty liver. A fatty liver cannot function properly and is a disease condition by itself. As more glucose is presented to the liver, it starts to make more fat and sends it out all over the body. The fat that forms inside the abdomen is called visceral fat. The accumulation of visceral fat leads to obesity.
The excess glucose is also converted to triglycerides and LDL, the “bad cholesterol.” The High -density lipoprotein, also known as the “good cholesterol,” is decreased. The combination of high triglyceride and low HDL (dyslipidemia) contribute to blood vessel damage, hypertension, atherosclerosis, and cardiovascular diseases.
Fatty Pancreas
The visceral fat infiltrates other solid organs like the pancreas and causes fatty pancreas. A fatty pancreas is dysfunctional and contributes to the development of Type 2 diabetes with all its complications.
Obesity and Systemic Inflammation
Fat also gets deposited around the intestines. The visceral fat comes with white blood cells called monocytes to fight any infections or foreign invaders that may pass the protective barrier of the gut. However, there are times when the wall becomes interrupted, and a “leaky gut” develops. This leads to unwanted chemicals, microbes, and drugs to leak outside the intestines to cause damage.
When that happens, the monocytes become activated and turn into macrophages for damage control. The macrophages call for reinforcements to go to war with the intruders and ask for help by producing hundreds of different kinds of signaling proteins called pro-inflammatory cytokines. The cytokines like interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFα) get to the war zone thru the blood vessels in the abdomen. However, the cytokines also get into the systemic circulation and spread to the whole body and spread the inflammation to other organs.
Effects of High Blood Sugar – ROS and AGE
High blood sugar in the cells, together with the inflammatory cytokines, leads to the production of negatively charged particles called reactive-oxygen species (ROS). The ROS is unstable and causes damage to other molecules within each cell, including the power supply of the cell (mitochondria). A situation that compromises cellular function. Just imagine how useful your cell phone is when it has a low battery charge.
ROS reacts with critical nitric oxide to make it lose its beneficial effects on the blood vessel lining.
Hyperglycemia also reacts with amino acids and fatty acids in the different organs of the body and produces advanced glycation end-products (AGEs). The AGE is similar to the sticky, brown coating of barbecued meat slathered with a sugared sauce. That is because the Maillard reaction happens in both. However, that AGE that forms inside the body is not as yummy but causes irreversible damage to the organs.
Hyperinsulinemia
There are about 200 cells in the body with insulin receptors. In hyperinsulinemia, all of these cells are exposed to high insulin levels, but they may not be insulin resistant like the muscles and the liver at the same time. Therefore they allow excessive insulin to work. Since insulin promotes storage and growth, HI leads to unwanted growth of cells in the skin producing skin tags and the prostrate causing an enlarged prostate. This vital article gives more detail about the systemic effects of hyperinsulinemia.
Obesity, dyslipidemia, hypertension, and high blood sugar are all included in the criteria for metabolic syndrome.
A Deadly Combination
Hyperglycemia, HI, ROS, AGEs, dyslipidemia, and the inflammatory cytokines all contribute and interact with one another to produce various illnesses in different organs. The diseased organs present in a way that differs from the other organs. That makes metabolic syndrome present in different ways. Some diseased organs like the liver and pancreas then go on and produce more diseases.
This article is just a bird’s eye view of the disastrous effects of insulin resistance. Looking back to the cause of IR, it all stems from a sedentary lifestyle and a bad diet. It is no wonder then that all the guidelines for obesity, hypertension, cardiovascular disease, and Type 2 Diabetes all recommend lifestyle changes before starting any medications.
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Photo Credits:
- Fatty Liver: The original uploader was Countincr at English Wikipedia. (Original text: National Digestive Diseases Information Clearinghouse) – https://catalog.niddk.nih.gov/catalog/ImageLibrary/detail.cfm?id=154, Public Domain, https://commons.wikimedia.org/w/index.php?curid=2310132
- Obese Man By FatM1ke – Central_Obesity_011.jpgCentral_Obesity_008.jpg, Public Domain, https://commons.wikimedia.org/w/index.php?curid=4412552
- Cytokines By Manu5 – http://www.scientificanimations.com/wiki-images/, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=77708936
- Free Radicals By Dan Cojocari – Own work, CC BY-SA 4.0, https://commons.wikimedia.org/w/index.php?curid=46529393
- Beer Belly By Diabetes – Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=65981665
- YouTube from Guinness World Records
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