What Is Gluconeogenesis and Why Is It Important?

Gluconeogenesis is a crucial metabolic pathway needed to produce glucose from noncarbohydrate sources such as amino acids, ketone bodies, and certain fatty acids. 

The process of gluconeogenesis explains why those adapted to a low-carb diet or prolonged fasting don’t tend to develop low blood sugar levels despite not consuming carbs or sugars. 

Here’s why you don’t need carbs or sugars to maintain blood sugar balance.

What is gluconeogenesis?

Gluconeogenesis occurs mainly in the liver and refers to a metabolic pathway that supports steady blood sugar levels by stimulating glucose production in the absence of dietary carbohydrate intake.

Most cells in the body can utilize non-glucose fuel sources, including ketone bodies. However, specific cells, such as red blood cells, the cells in the retina, and certain parts of the brain, require blood glucose to function. 

Hepatic gluconeogenesis serves as a backup mechanism to ensure these cells receive adequate glucose if no carbohydrates are available and glycogen stores are depleted. 

Gluconeogenesis and hepatic glucose output are complex metabolic processes tightly regulated by pyruvate kinase and pyruvate carboxylase. These two gluconeogenic enzymes are sensitive to hormonal signaling and respond to free glucose concentrations in the blood.  

Why you don’t need to consume carbs

There is a common misconception that carbs are an important fuel needed to maintain steady blood sugar levels. 

However, this isn’t accurate. When liver cells sense a drop in carbohydrate metabolism, meaning no carbs are available to maintain the blood glucose level needed to promote normal physiological function, gluconeogenesis occurs.  

The gluconeogenesis pathway can synthesize glucose from various compounds, including lactate, glycerol, and odd-chain fatty acids, to maintain plasma glucose concentration.

In addition, several glucogenic amino acids can be converted into intermediates of the citric acid cycle or pyruvate, which can then be converted into glucose through several biochemical reactions.

Gluconeogenesis explains why individuals who have adapted to a low-carb diet or fast for prolonged periods can maintain stable blood glucose levels without consuming sugars or carbs. 

Watch the video below to learn more about gluconeogenesis. 

Gluconeogenesis and insulin resistance

Insulin plays a vital role in regulating gluconeogenesis. Poor metabolic health, such as cellular resistance to insulin, also known as insulin resistance, can significantly interfere with normal blood sugar control.

Insulin is a hormone released in response to carbohydrate intake. It signals muscle cells to absorb blood glucose, which enables energy production and helps maintain steady blood sugar levels. 

However, chronically elevated insulin levels, typically linked to a high-carb diet, can cause cells to become desensitized to its signaling. This can result in insulin resistance and a lack of cellular glucose uptake.

When liver cells become insulin resistant, they cannot absorb and metabolize blood sugar, which triggers gluconeogenesis despite already elevated blood glucose levels. This causes a vicious cycle of hepatic glucose production, elevated insulin levels, and worsening insulin resistance. 

Because insulin resistance triggers gluconeogenesis despite ample glucose being available, it can quickly progress into prediabetes or diabetes, characterized by elevated blood glucose levels and a loss of blood sugar control. 

According to research published in Endocrine Disorders, more than 40 percent of U.S. adults have some degree of insulin resistance. This leaves a large proportion of the population at risk of diabetes and other serious metabolic disorders, including obesity, high blood pressure, and heart disease.

What is the dawn phenomenon? 

The dawn phenomenon refers to a natural rise in blood glucose levels in the early morning, typically two to three hours before waking.

As sleep cycles progress, the body releases cortisol and glucagon. These hormones stimulate gluconeogenesis to provide the body with energy during the waking hours.   

Most people experience a small and well-regulated rise in blood sugar levels while sleeping. However, those with insulin resistance and diabetes can develop significantly elevated blood glucose. 

The dawn phenomenon can make it difficult to successfully manage blood sugar levels for those taking anti-diabetic drugs or insulin. This can speed up disease progression and increase the risk of diabetic complications such as vision loss and nerve damage. 

A study published in Scientific Reports investigated the health consequences of poor blood sugar management. The authors summarized, “The long-standing effects of hyperglycemia are associated with long-term damage, dysfunction, and failure of different organs, especially the eyes, kidneys, nerves, heart, and blood vessels.”

If you monitor your blood glucose levels to manage or prevent diabetes and notice consistently elevated blood sugar levels in the morning, it’s essential to consult a healthcare provider. 

Glucose tolerance and fasting insulin tests can help evaluate blood glucose control, which can guide appropriate medication adjustments and dietary changes.   

Improving dawn phenomenon related to gluconeogenesis

High blood sugar levels in the morning are common, especially in individuals with metabolic imbalances, insulin sensitivity, and poor blood sugar regulation. 

Research published in Endocrine Practice found that more than 50 percent of diabetic patients experience the dawn phenomenon due to upregulated gluconeogenic processes.   

While there are currently no approved treatment options, making beneficial dietary changes to promote balanced blood sugar and insulin levels is critical in supporting metabolic health. 

Here are two steps you can take to improve elevated blood sugar levels in the morning.

1. Practice intermittent fasting 

Intermittent fasting is a mealtime schedule that cycles between periods of fasting and time-restricted eating windows.

Prolonged periods of caloric restriction contribute to maintaining stable blood sugar levels. This, in turn, keeps insulin levels low, which is vital for enhancing insulin sensitivity.

A study published in Molecular Metabolism found that fasting for as little as 12 hours caused a significant decrease in blood glucose and plasma insulin levels. 

Improved cellular insulin signaling combined with stable blood glucose levels promotes balanced gluconeogenesis. This is linked to better overall blood sugar control and may benefit individuals affected by the dawn phenomenon. 

2. Limit carbohydrates  

Carbohydrates and sugars are rapidly digested and contribute to spikes in blood sugar and insulin levels. 

Limiting carbohydrates and obtaining the majority of calories from healthy fats can help keep blood sugar and insulin levels stable, thereby reducing the risk of insulin resistance and the dawn phenomenon. 

A high-fat ketogenic diet limits daily carb intake to no more than 50 grams of net carbs daily. 

“While carb restriction stimulates gluconeogenesis, keto is a highly effective strategy to manage and even reverse insulin resistance,” explains Dr. Berg. “This makes a high-fat diet one of the best dietary approaches to improve elevated blood glucose levels in the morning.”    

By restricting carbohydrates, the glucose load entering your bloodstream is kept low. This can contribute to more stable blood sugar levels during the night and early morning hours.

Key takeaways

Gluconeogenesis is a metabolic pathway that ensures specific cells and tissues can utilize blood glucose as an energy source if no dietary carbohydrates are available.  

However, those with insulin resistance often have overactive gluconeogenic pathways, which can contribute to abnormally high blood sugar levels in the morning, also referred to as the dawn phenomenon. 

Practicing intermittent fasting and limiting carbohydrate intake by following a low-carb ketogenic diet is an excellent strategy to promote balanced gluconeogenesis and stable blood sugar levels. 

FAQ

1. What is gluconeogenesis?

Gluconeogenesis is a metabolic process that ensures stable blood sugar levels when dietary carbohydrates are unavailable. 

The liver can convert certain amino acids and fatty acids into glucose, which is released into the bloodstream. This plays a vital role in ensuring the proper functioning of glucose-dependent cells, including specific brain cells, red blood cells, and the cells in the eye’s retina.  

2. Is gluconeogenesis fasting?

Yes, fasting triggers gluconeogenesis. Caloric restriction can quickly deplete blood sugar and glycogen stores, which pushes the body to convert amino acids and fatty acids into glucose. 

This is an important process to prevent dangerously low blood sugar levels when dietary carbohydrates are unavailable, such as during fasting periods.

3. What is the dawn phenomenon?

The dawn phenomenon refers to abnormally high blood sugar levels during the early morning hours. 

Individuals with insulin resistance or diabetes are often affected by the dawn phenomenon. It’s believed that poor blood sugar control and hormonal imbalances can upregulate gluconeogenesis, leading to excessive glucose production while sleeping.  

4. Does the body make sugar?

Yes, the body can produce glucose from amino acids and certain fatty acids through a metabolic process known as gluconeogenesis. 

5. Why is my blood sugar still high even though I’m not consuming sugar?

Elevated blood sugar levels in the morning, despite not eating sugar, can indicate insulin resistance. 

When cells don’t respond to insulin, blood sugar isn’t absorbed into cells, signaling the liver to produce glucose by triggering gluconeogenesis. This explains why those with insulin resistance and diabetes are more likely to experience elevated blood sugar levels even if they don’t consume carbs or sugars.   

6. Is it normal to have high blood sugar in the morning?

It's not uncommon for blood sugar levels to be higher in the morning as this is a natural hormonal response to provide the body with energy during the waking hours.   

However, consistently high blood sugar in the morning can indicate underlying health issues such as insulin resistance or uncontrolled diabetes.

Sources

1. https://bmcendocrdisord.biomedcentral.com/articles/. 

2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10267215/ 

3. https://www.endocrinepractice.org/article/S1530-891X(20)39957-2/  

4. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7471620/