Fatty Liver, Insulin and Glucose Metabolism

I decided to write this article to connect concepts in other articles I have written, but I also wanted to demonstrate how sugar and insulin drive metabolic syndrome and fatty liver disease, and not fats which are often made out to be the bad guys.  This is part of metabolic syndrome which is a subject to big to discuss in one article.

In very simple terms, if you eat a lot of sugar, carbohydrates, grains or starches, and you don’t exercise enough to burn this off, your blood sugar levels will go up, right?  Your liver acts like a storage unit, so with all this sugar in the blood and nowhere to go, the liver will suck it up and store it as glycogen.  When the liver is full and there’s no more space for more sugar it will change the sugar to cholesterol and spit it back out into the blood to go store somewhere else as fat.  Some of this fat can also store in the liver, known as fatty liver.  This is the short explanation.

Now.  For those of you who want to know how this works…


GLUCOSE METABOLISM:  Glycation and Methylation


So how is blood sugar controlled?  There are 3 hormones that are directly responsible for blood sugar control:

Insulin is produced in response to an increase in blood glucose levels and converts it to either glycogen in the muscles and liver (glyconeogenesis) or fat (lipogenesis).  According to Mike Julian your body should never have to rely on insulin alone to clear glucose from the blood.  If you get to this stage then your are in trouble.

Glucagon is produced in response to a drop in blood glucose levels and converts glycogen (stored glucose) back into glucose (glycogenolysis) or stimulate amino acid/protein conversion into glucose (gluconeogenesis).  This often occurs when there is stress, inflammation or sympathetic activation of the nervous system.

Glucocorticoids are produced when blood sugar is low or when ACTH is released from the hypothalamus in response to stress or sympathetic activation.  They initially reduce inflammation, provide stress resistance, depress the immune system and increase blood glucose by breaking down protein (gluconeogenesis) and fat (lipolysis).


What happens when someone follows a high carbohydrate or sugar diet, or they have high blood sugar levels for other reasons…



The higher the blood glucose, the more insulin is secreted by the pancreas in an effort to open the GLUT receptors and allow glucose to enter the cells to be burned for energy inside the mitochondria.  But when there is inflammation inside the cell as seen in chronic disease or the CDR (Cell Danger Response), GLUT translocation to the cell surface will be down-regulated.  When the GLUT receptors fail to translocate to the cell membranes or the insulin receptors become blunted/unresponsive we get insulin resistance.  At this point it doesn’t matter how much insulin the body secretes, the cells simply do not respond.

There are two exceptions to this and it is the liver and the brain.  These two organs can absorb glucose into their cells without insulin or GLUT transporters as part of a survival mechanism.

We see insulin resistance as the problem and do our best to get insulin to respond, but maybe we should consider that this is an evolutionary protective mechanism to protect cells from an over-influx of glucose into the cells.  It could be a real case of having too much glucose inside the cell due to a high GI meal, or as part of mitochondrial dysfunction where the mitochondria is unhealthy and cannot burn large amounts of glucose even within ‘normal’ limits.  Once glucose enters the cell and is converted into glucose-6-phosphate it cannot leave the cell.  This is an irreversable conversion, so insulin resistance protects the cells from allowing any more glucose into the cells after glucose-6-phosphate levels are saturated.

Remember that the metabolism of glucose into energy/ATP produces a lot of free radicals in the process.  If the body cannot cope with this it will do everything in its power to stop more free radical production as this will eventually lead to cell death.  The body’s first priority is always survival.  At this point it will slow down and alternative routes will have to be found to get rid of the excess glucose.



High levels of glucose in the blood will keep stimulating insulin production without any effect.  So now the liver has to make Insulin Binding Globulin (IBG) to bind all this excess insulin being secreted due to insulin resistance (at least in the early stages before the pancreas becomes exhausted) which requires energy.  If energy is being conserved as in the case of the CDR then liver function will suffer, less IBG will be produced, more unbound insulin will circulate causing blood sugar to drop and cause reactive hypoglycaemia.



This is the process by which the liver will start to break down glycogen (stored glucose) or amino acids (protein and muscle) to produce glucose.  This happens when there isn’t enough glucose for energy production or when the body THINKS there isn’t enough glucose for energy production as in the reactive hypoglycaemia example above.  In the latter case you can end up with something called glucotoxicity.

Reasons for a drop in blood sugar and gluconeogenesis signalling include:

  • Endurance exercise (this will usually only happen in exercise lasting longer than an hour)
  • Fasting
  • Starvation
  • Low carb/sugar diets
  • Reactive hypoglycaemia



When very little insulin is secreted by the pancreas, even if blood sugar is high, the liver will interpret the low insulin secretion as a sign that there isn’t enough glucose for energy production and will start to make more.  This can really spike blood sugar levels up a lot which will cause damage to the pancreatic β-cells and eventually lead to type 1 or insulin-dependant diabetes through the glycation process.

The excess glucose is transported to the liver which activates fat synthesising enzymes in response to the higher concentrations of glucose.  These fat synthesising enzymes will produce fatty acids such as palmitic and palmitoleic acid from glucose.  Free fatty acids combine to form triglycerides (3 fatty acids combined with glycerol).  Some of if will be stored inside the liver cells and produce fatty liver, and some of them will be transported back into the blood as free fatty acids and triglycerides.  We expand on this further down.



So now you have lots of fuel – lots of glucose (high blood sugar) and lots of free fatty acids (liver making it from glucose).  All this fuel has to be burned for energy in the mitochondria.  This will put tremendous nutritional strain on the mitochondria and whatever does not make it down the oxidative phosphorylation pathway (krebs cycle) will be shunted into the glycolytic pathway producing sorbitol (diabetes, cardiovascular disease, nerve damage), lactate (muscle pain, fibromyalgia, fatigue), purines (gout) and glyoxylation products (damaged proteins).

Not just that.  The mitochondria is now working faster to try and burn of this excess fuel and in the process produces free radicals (ROS – reactive oxygen species).  If these are not dealt with by dietary antixodants (good diet, vegetables) or the body’s endogenous antioxidants (SOD, Glutathione for which you need healthy methylation) then they will further damage blood vessels, cells and mitochondria which will slow this energy burning process down and make weight loss even harder.

This is why healthy mitochondria is so important in weight loss!


The role of sugar in fatty liver and metabolic syndrome.



You can imagine the krebs cycle as being a spinning wheel.  By adding more fuel (glucose) you are spinning this wheel faster and faster (if the mitochondria is well enough or able to) to produce energy/ATP.  As the cycle is spinning and using up fuel, it also spits out other intermediary products that’s needed elsewhere in the body.  Citrate is one of the intermediary products produced during the krebs cycle, and citrate is needed for fatty acid synthesis.  That’s right, making more fats.



Statins stop the liver from making cholesterol and turning glucose into fat.  This gives your liver no choice but to send all the excess glucose back into the blood stream.  So you may have great cholesterol levels, but your blood sugar will be higher, glycation will increase causing damage to the blood vessel walls and kidneys, and your risk for heart disease will keep on increasing (and now diabetes too) whilst you’re under the false impression that statins are helping you prevent this.  It is very important that you monitor your blood sugar, insulin and HbA1c levels while on statins, as well as reducing your dietary carbohydrate and sugar intake.



Cholesterol medication will also interfere with vitamin D production in the body as vitamin D is synthesized from cholesterol, as well as CoQ10.  Vitamin D is responsible for immune regulation and has been linked to auto-immune disease and thus type 1 diabetes.  But the pancreas is also rich in vitamin D receptors (VDR).  So vitamin D docks onto these VDR’s which sends the message to the pancreatic β-cells to produce insulin.  Insulin removes excess glucose out of the blood stream.  If vitamin D is deficient as a consequence of statin use, then these receptors don’t function properly, insulin is not produced and blood sugar spikes.

Vitamin D is also needed for muscle strength and growth, and the muscles determine the metabolic rate in the body.  The more muscle you have the faster your metabolism (athletes) and the less muscle mass you have the slower your metabolism (obesity).  This is because muscle cells contain lots and lots of mitochondria to produce energy for muscles to work hard.  If muscles atrophy because of vitamin D deficiency and the mitochondria is sluggish because of CoQ10 deficiency, we’re going to end up with a lower metabolic rate, slower burning of carbohydrates, sugars and fat, and increases in blood sugar and weight gain.

In the absence of vitamin D calcium is released from the bone into the blood to keep electrolytes balanced.  When calcium is higher than magnesium in the bloodstream it can lead to vascular constriction and increased blood pressure which raises the risk of cardiovascular disease.  Reduced heart mitochondrial function and heart muscle function due to CoQ10 deficiency may contribute to this further.



In acute stress (fight-or-flight) insulin levels will drop and blood glucose will increase.  This is to allow more glucose in the bloodstream for quick energy production in order to ‘escape’ the dangerous situation and is a temporary survival mechanism that will revert back to normal when the stress is gone.  The longer this situation goes on, the more sensitive the pancreatic B-cells will become to glucose.  If the stress becomes chronic (longer than 30 days according to rat studies) then even smaller amounts of glucose will set off the release of large amounts of insulin as the pancreas becomes more responsive to glucose.

This could explain why some lose weight in the initial stages of stress, but eventually start to put weight on.

Increases in insulin will increase glucose absorption into the cells and stimulate fat production, at the same time slowing down the breakdown of existing fat stores in the body.



So we now know what happens when there is too much glucose for cells to absorb (glucotoxicity), but what if there is too many fatty acids?  Fatty acids can come from a high fat diet or through increased fatty acid production as already explained.  When the liver is exposed to higher concentrations of fatty acids it starts to produce more fat-carrying lipoproteins such as ApoB which carries VLDL and TG’s into the bloodstream.  HDL and LDL also become more saturated with these extra fats, and this is what contributes to cardiovascular disease and plaque formation in the blood vessel walls.

This does not happen on a high fat LOW CARBOHDYRATE diet which is why it is very important to decrease carbohydrate intake when you increase your fats.  If you start consuming healthy fats such as coconut oil, eating more bone broths, butter and ghee, and you’re still consuming your usual amounts of high glycemic carbohydrates, don’t be surprised if your blood glucose and lipid readings look worse next time you have them tested.  Don’t blame the fats, blame the carbohydrates.


If you need guidance in the treatment of this or any other condition, please make an appointment with one of our practitioners.

This article is for information purposes only.  Please refer to our Medical Disclaimer policy for more information.  The opinions expressed here represents the author’s and not necessarily those of Realize Health.  In addition, thoughts and opinions change from time to time due to updates in research and as a necessary consequence of having an open mind.  Views expressed in out-of-date posts may not be the same to those we hold today.



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Effect of chronic psychological stress on insulin release from rat isolated pancreatic islets

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Elizma Lambert

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