How the liver works (related to glucose levels)

Here’s a good paper on how the liver works (Compr Physiol. Energy Metabolism in the Liver. Liangyou Rui). The paper is technical but it covers the role of the liver in handling fat, carbs and protein. Fed and fasted states are discussed.

This is of particular interest to diabetics:

Aberrant energy metabolism in the liver promotes insulin resistance, diabetes, and nonalcoholic fatty liver diseases (NAFLD)…. Dysfunction of liver signaling and metabolism causes or predisposes to nonalcoholic fatty liver disease (NAFLD) and/or type 2 diabetes.

The sugar in your blood comes from your liver. It either comes from glycogen stores or when the glycogen runs out, from other sources in the body. On the subject of glucose levels in the blood:

During short-term fasting periods, the liver produces and releases glucose mainly through glycogenolysis.

So, overnight the liver produces glucose from glycogen via glycogenolysis. Glycogenolysis is:

Glycogenolysis is the breakdown of glycogen (n) to glucose-6-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase. (Wikipedia).

Liver glycogen provides about 400 calories or 100 grams of glycogen (PLoS Comput Biol. 2011 Dec; 7(12): A Whole-Body Model for Glycogen Regulation Reveals a Critical Role for Substrate Cycling in Maintaining Blood Glucose Homeostasis. Ke Xu, Kevin T. Morgan, Abby Todd Gehris, Timothy C. Elston, and Shawn M. Gomez):

Blood glucose is provided from absorbed carbohydrates during feeding up until digestion is complete, at which point hepatic glycogen stores take over this role. Depletion of hepatic glycogen occurs over a period of 12–24 hours, though this varies greatly with activity levels.

Next comes gluconeogenesis.

Once hepatic glycogen stores are consumed, blood glucose levels are maintained by gluconeogenesis. This process uses energy derived from storage fat in the form of acetyl CoA and the carbon skeletons of glycogenic amino acids.

GNG happens in:

The major sites of gluconeogenesis are the kidney and the liver, with only the latter being represented here. As blood glucose levels fall due to hepatic glycogen depletion, blood insulin levels fall while glucagon levels rise, leading to biochemical changes resulting in the use of alternative fuels in the form of free fatty acids and ketones, and gluconeogenesis…

One way to potentially lower blood glucose is to fast the body until the liver glycogen stores are depleted. This could be done with one longer fast (more than 24-hours) or by several days in a row of intermittent fasts. Each day of the intermittent fast will leave the liver with less glycogen until the glycogen stores are lower. Eating very low carbohydrates helps this process.

Back to the original paper on the liver.

During prolonged fasting, glycogen is depleted, and hepatocytes synthesize glucose through gluconeogenesis using lactate, pyruvate, glycerol, and amino acids…These gluconeogenic substrates are either generated in the liver or delivered to the liver through the circulation from extrahepatic tissues.

Here’s a really good paper on the above and the ketogenic diet (McDonald 1996, Chapter 3. The basics of fuel utilization.).


Author: Doug

I'm an Engineer who is also a science geek. I was pre-diabetic in 1996 and became a diabetic in 2003. I decided to figure out how to hack my diabetes and in 2016 found the ketogetic diet which reversed my diabetes.

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