Glucose Metabolism: What It is, How It Works and Why We Need It

Many “thought-leader” bloggers, social media wellness influencers, and even some credentialed medical professionals espouse the benefits of kicking all sugar to the curb. Stat.  

It’s addictive. It messes with your hormones and increases cravings. It makes you fat. 

Sugar (glucose) can be associated with all of these statements. However, understanding sugar, glucose metabolism, and how your body processes glucose provides foundational knowledge to help you make informed decisions about what’s best for you. It is even more important if you live with chronic illnesses such as diabetes mellitus, hyperglycemia, or metabolic syndrome.

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What is Glucose Metabolism?

Glucose metabolism is the process that cells in the human body use for nourishment and energy. Glucose metabolism begins with the digestion of carbohydrates. The primary role of carbohydrates is to supply energy for your body's cells. Complex carbohydrates are broken down into simple sugars, such as glucose and fructose. When your cells need energy, bonds between carbon atoms in glucose are broken to release energy that your cells can use. 

Since many cells preferentially use glucose for energy, your body can also convert amino acids from proteins and fatty acids into glucose. Excess glucose is stored as glycogen, primarily in the liver and muscles.¹

How Does the Body Process Glucose?

Glucose is a simple sugar. It’s present in the blood (often called blood glucose) and is a major fuel source for organs, tissues, and metabolic processes. 

When we eat sugar, our bodies convert it to glucose to use as a source of energy. As carbohydrates enter the bloodstream, the pancreas releases insulin to be a glucose transporter and shuttle the glucose to the cells for energy or storage. After blood glucose levels reach a post-meal peak, glucose slowly decreases over several hours and returns to fasting levels. Immediately after a meal, glucose removal into the skeletal muscles and adipose tissue is driven by insulin.¹³

Dietary fat and protein can affect your blood glucose as well. Fat isn’t broken down like carbs; it’s broken down slowly into fatty acids. A high-fat meal may have a minimal effect on post-meal glucose and insulin; however, animal research has associated a high-fat diet with an increased risk of insulin resistance.²

While protein is broken down similarly to carbs, it affects blood glucose differently. Protein digestion begins in the stomach and continues in the intestines, where it’s broken down into amino acids. In the liver, some amino acids convert to glucose while others are used to make protein again for muscle use. When adequate insulin levels are present, protein can have a minimal effect on glucose levels. 

Glucose, the body’s preferred source of metabolic fuel, is most readily available from carbohydrates. When carbs are restricted, your body can make glucose from fat (from glycerol) and protein (from the amino acid glutamine) through gluconeogenesis.

Cells' Role in Our Organism?

Glucose metabolism entails the process of glucose entering the tissue cells and converting into adenosine triphosphate (ATP). Glycolysis, the process by which carbs are broken down to produce energy, occurs in the cytoplasm of the mitochondria when one glucose molecule is broken down to form pyruvate to synthesize ATP molecules. 

The body's energy currency, mitochondrial ATP, is used to transport molecules across cell membranes, contract muscles, conduct nerve impulses, divide and grow cells, and create reactions that make hormones, cell membranes, and other vital molecules. 

Why is Glucose Metabolism Important?

The body prefers glucose as an energy source. Organs that use glucose as a source of fuel include:

• Brain: Glucose is virtually the sole fuel for your brain, except during prolonged starvation. The brain doesn't store fuel, so it requires a steady stream of 120 grams of glucose daily.³ This amounts to about 420 calories.  
• Muscles: Major fuels for the muscles include glucose, ketones, and fatty acids. About three-fourths of all glycogen gets stored in the muscles. Glucose is the preferred source of fuel to power bursts of activity. 
• Adipose tissue: This is the fat tissue that most of us loathe. Fat cells need glucose for the creation of triacylglycerols, these cells' main energy storage resource. The glucose level inside fat cells helps determine whether fatty acids are released into the blood for energy use.
• Kidneys: Glucose is reabsorbed as part of the kidneys' process of filtering blood plasma about 60 times each day. During starvation or when glucose isn't readily available as an energy source, the kidneys may synthesize glucose through gluconeogenesis.
• Liver: Your metabolic hub, the liver, is involved in glucose production and releases glucose into the blood by breaking down its glycogen store and carrying out gluconeogenesis. In a fasted state, the liver converts fatty acids into ketones.

The body needs glucose for normal functioning. The source of glucose can come from dietary carbohydrates, or the body can produce glucose through gluconeogenesis. When little to no dietary carbohydrates are available, ketones can become an energy source for the body.

Negative Implications of Sugar Metabolism Malfunction

Several potential disconnects with glucose metabolism can lead to malfunctions and severe symptoms. These include:

• If a cell membrane dries up and loses fatty acids, the integrity of the cell will be compromised, and die
• Insulin receptors could be deficient and not send clear signals to the body. 
• PPARs (receptors in a cell nucleus) could be deficient in omega-6 fatty acids. 
• The pancreas may not be producing insulin and impact signals to the body. 
• The pancreas could be damaged or not secreting insulin at all.

To ensure that glucose metabolism is taking place properly in your body, you should test your blood sugar levels regularly, work with your healthcare provider, and eat balanced meals.

Glucose Metabolism and Diet

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Muscle cells absorb most excess blood glucose as long as they are sensitive to insulin. When muscle cells become inflamed from excess fatty acids, the liver picks up excess glucose. If glycogen stores are full, excess glucose in the liver is stored as fat. Free fatty acids increase in the blood, which makes the liver and muscle more insulin resistant.¹⁴

A small study of 22 obese, prediabetic participants compared the effects of a low-glycemic diet and exercise plan with a high-glycemic diet and exercise regimen. While both groups lost equal amounts of body weight and showed improvement in insulin sensitivity, the low-glycemic diet group saw reduced post-meal hyperinsulinemia (a condition where the amount of insulin in the blood is higher than what’s considered normal).¹¹

Exercise benefits glucose stabilization; research shows that it can restore glucose metabolism in insulin-resistant muscles and improve insulin sensitivity for up to 48 hours after the workout.¹² This awareness helps contextualize the study's results on the impact of the high-glycemic vs. low-glycemic diet, which both asked participants to exercise.

It’s also important to note that many of the studies reviewing the glycemic effects and impact on body weight and other health markers tend to test prediabetic, diabetic, and overweight or obese individuals. This makes sense as researchers try to find solutions to help populations with diseases or disorders. 

These studies provide general insight for healthy people who want to lose weight or prevent the negative implications of poor glucose metabolism. However, specific insulin, glucose tolerances, and glucose responses may differ in healthy people compared to those with diabetes or metabolic syndrome. 

Glucose Metabolism vs. Weight Loss

Weight loss only tells us we carry less mass throughout our bodies. We may notice a lower number on the scale, but how did we get there?

Our weight can fluctuate, even daily, and these weight swings can occur due to various factors. We may see changes in weight resulting from hormonal imbalances, varying sodium intake, and fiber consumption. When weight loss occurs under such circumstances, it can encompass water, muscle, and fat loss.

Recently, there has been a shift to ketogenic (keto) or low-carb eating styles to lose weight. A 2013 meta-analysis of studies reported that very low-carb diets (less than 50 grams per day) could work for weight loss in the long term.⁷ The catch: Keto and low-carb diets can be hard to sustain. 

Carbohydrates provide a quick and easily metabolized source of glucose that can lead to a rise in blood glucose (blood sugar). Provide the body with a steady stream of its preferred fuel source, carbs, and the body uses what’s currently needed for energy and stores the remaining glucose in the muscles and liver. When those stores are full, any excess glucose gets stored in adipose tissue as fat. 

Very low-carb diets encourage burning through stored glycogen in a few days or less at the start of the regimen. After that, your body uses the relatively small amount of carbs you might get from your diet for energy first; then, it digs into your stored body fat for fuel. This is why keto and low-carb dieters can lose weight, sometimes rather quickly, and see improvements in their proportion of body fat to lean mass. 

If you don’t allow your body to burn through its glucose stores, you won’t burn through any stored body fat. If you’re happy with your weight and body composition, you may not see a reason to burn stored fat, or you may not have a lot of stored fat to lose (lucky you!). 

If you want to lose weight and burn fat, it’s a different story. To lose body fat, you’ll have to make some changes to your eating habits and integrate exercise into your regimen. 

Can Ketones Replace Glucose?

Not exactly. The body requires glucose to function. While the body can make ketones for energy when necessary, the body still needs glucose. For example, red blood cells lack mitochondria and can’t use ketones for fuel. 

The body requires some blood glucose to keep us alive and awake. If blood glucose drops below 70 mg/dL, you could feel dizzy, confused, shaky, and like you might pass out. Some worry that hypoglycemia could result from a severe dip in blood glucose, but it’s a condition that’s rare in non-diabetics who don’t take insulin. 

So, how do our bodies meet our need to keep blood glucose up when we’re not eating (fasting)? Where could an energy source come from if our diets do not supply it? In a word, ketones.

Ketones are molecules formed in the liver from fatty acids and some amino acids when the body doesn’t produce enough insulin to convert glucose into energy. 

This can happen in a fasted state, while intermittent fasting, or for longer stretches when we don’t take in fuel. This can also happen during a ketogenic diet when severe carb restriction requires the liver to convert fat into an energy source. 

During times of low energy availability, like fasting or starvation, gluconeogenesis creates glucose from amino acids (protein), the breakdown of structures such as muscle tissue, and glycerol and free fatty acids are created through lipolysis and provide the energy for gluconeogenesis.⁴ Although most tissues can hydrolyze glycogen, only the liver and kidneys contain glucose-6-phosphate, an enzyme necessary to release glucose in the cardiovascular system.

Normally, our bodies rely on sugar first for energy. Once the glucose concentration in our bloodstream is used up, our bodies can tap into glucose stored in the muscles and liver. Once those stores are depleted, fat stored in our adipose tissue is used for fuel. When that’s not available, ketones provide backup to ensure the body is in glucose homeostasis.

Ketones are released into the bloodstream and taken up by your organs, including your brain, moved into the mitochondria, and used as fuel. Excess ketones are excreted through urine, and acetone (a type of ketone) is released in the breath. 

Some high-glycemic foods (and maybe even moderate-glycemic foods) can cause rapid rises and dips in blood glucose—sometimes multiple times after one glucose-spiking meal—that requires the liver to release a proportional amount of insulin to shuttle the glucose to where it can be used for energy.  

Over many years, spiking and dipping glucose levels can lead to insulin resistance, weight gain, obesity, metabolic syndrome, prediabetes, or even type 2 diabetes.⁶

FAQs Around Glucose Metabolism 

What are the main stages of glucose metabolism?

Glucose metabolism involves multiple processes, including glycolysis, gluconeogenesis, glycogenolysis, and glycogenesis. Glycolysis in the liver is a process that involves various enzymes that encourage glucose catabolism in cells.¹⁴

What is the name of the hormone that stimulates glucose metabolism?

Insulin and glucagon are the key hormones in glucose metabolism. Glucagon helps prevent blood sugar from dropping, while insulin stops it from rising too high. Insulin secretion also stimulates fat synthesis, promotion of triglyceride storage in fat cells, promotion of protein synthesis in the liver and muscles, and cell growth.

What is the difference between aerobic and anaerobic glucose metabolism?

Aerobic metabolism generates more ATP and relies on oxygen. However, anaerobic metabolism does not need oxygen and creates two ATP molecules per glucose molecule. Both processes are required to produce cellular energy.

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