Insulin Resistance and Gluconeogenesis

author avatar Dr. Eric Berg 04/05/2024

Not many people fully understand the world of insulin resistance and gluconeogenesis, even though they are very important topics for health-conscious individuals to be aware of.

Learn about how insulin works in your body, what effects it can have, and how you can promote healthy levels of insulin sensitivity.

The Role of Insulin in Glucose Metabolism

Under normal conditions, insulin signaling facilitates glucose uptake by binding to its receptor on cell surfaces. This is vital for maintaining balanced blood sugar levels.

However, problems arise with insulin resistance, where cells become less responsive or 'resistant' to insulin's action. Consequently, glucose can't enter these resistant cells quickly; instead, it builds up in your bloodstream leading to high blood sugar levels, which is a condition often seen before type 2 diabetes develops.

Hepatic Insulin Action and Resistance

Insulin reduces hepatic glucose production (gluconeogenesis) and stimulates the storage of excess nutrients in anabolic pathways such as glycogen synthesis.

In people with type 2 diabetes, their livers do not respond appropriately to insulin. This results in uncontrolled production of new glucose through gluconeogenesis, contributing significantly towards high fasting blood sugars.

The Process of Gluconeogenesis

Gluconeogenesis essentially means "making new" (-genesis) "glucose" (gluco-) from non-carbohydrate sources such as lactate or amino acids (proteins). Your liver undergoes this process when fasting or your carbohydrate intake is low.

The liver employs gluconeogenic enzymes, like PEPCK, to sustain blood sugar levels when a person is fasting or has low carbohydrate intake.

The Journey from Insulin Resistance to Diabetes

Insulin resistance is a condition that occurs when the body's cells become less responsive to insulin, causing high blood sugar levels. This condition can often lead to pre-diabetic states and, eventually, diabetes mellitus.

The Role of Pancreas in Insulin Production

The pancreas is essential in maintaining the proper sugar levels in our bodies, thus making it a key factor for preventing pre-diabetes and diabetes mellitus.

When we indulge in diets with high sugar intake, it compensates by producing more insulin. Research suggests this can be a double-edged sword leading to increased insulin resistance.

This overproduction works well initially as it helps keep blood glucose at bay. However, continuous exposure to these heightened amounts causes our cells' sensitivity toward insulin to drop dramatically.

Eating in a calorie deficitImpact of Diet on Insulin Resistance and Gluconeogenesis

Your food choices can significantly affect insulin resistance and gluconeogenesis. These two processes play vital roles in regulating blood sugar levels, with your diet being a major influencing factor.

The Paradox of Low-Carb Diets and Blood Sugar Levels

It might seem logical that reducing carbohydrate intake would lower blood sugar levels. After all, carbs break down into glucose which raises your blood sugar.

Despite the logical assumption that reducing carbohydrate intake would lower blood sugar levels, our bodies have a backup plan for energy production called gluconeogenesis.

Gluconeogenesis is our body's backup plan for energy production when carbohydrates are scarce. This metabolic process permits the liver to construct glucose from sources, not carbohydrates, such as fat or protein.

Even if you cut out carbohydrates completely, your body will still produce glucose through gluconeogenesis to keep essential bodily functions running smoothly.

So paradoxically, despite eating fewer carbs, people may not see their expected drop in blood sugar levels because of this compensatory rise via gluconeogenesis.

In some cases, drastically cutting carb intake could lead to higher-than-normal rates of gluconeogenesis, resulting in elevated fasting glucose levels.

Dietary Balance: Carbs vs Essential Nutrients

Maintaining a balance between consuming enough essential nutrients while controlling carbohydrate intake can be tricky. Still, it's vital for managing insulin resistance and other physiological systems' healthy functioning.

You don't want high sugar intakes driving up insulin demand, nor do you want nutrient deficiencies by over-restricting carbs.

Roughly 5% of people on an extremely low-carb diet see a rise in fasting glucose levels because gluconeogenesis increases. Plus, blood sugar control might get worse by up to 10%.

The Role of Gluconeogenesis in Diabetes

When it comes to managing diabetes, understanding the role gluconeogenesis plays is essential. Gluconeogenesis is a metabolic process in which glucose is synthesized from non-carbohydrate sources to maintain blood sugar levels when dietary intake isn't sufficient.

This process helps maintain blood sugar levels when dietary intake isn't sufficient.

Hormonal Regulation of Gluconeogenesis

Your hormones are crucial in regulating this intricate dance between insulin and glucagon. The hormone insulin inhibits gluconeogenic substrates while promoting glucose uptake by cells for energy use.

But what happens if there's too much glucose? That’s when glucagon steps up. When insulin levels increase, and glucagon secretion decreases, the liver's glucose production through gluconeogenesis is reduced, helping maintain stable blood sugar.

This careful hormonal regulation typically maintains stable blood sugars. But for those with diabetes, these checks and balances can go awry, leading to persistently elevated high blood sugar levels, a condition that poses significant health risks over time.

Gluconeogenic Substrates & Insulin Resistance

In chronic overnutrition or sedentary lifestyle cases often seen among diabetes patients, muscles become less responsive to insulin, causing what we call 'insulin resistance.'

High Blood Sugar despite Low Carb Intake?

You might think cutting down carbs would reduce your body's need for extra-insulin action and lower blood sugars – sounds logical, right? Not always.

The liver compensates for the perceived glucose shortage by ramping up gluconeogenesis, leading paradoxically to higher blood sugars. This increase can be so significant that it overrides the potential benefits of reducing dietary carbs.

But here's the thing, insulin resistance complicates how your body reacts to food. It's not merely a matter of 'what you consume.' Instead, it's more about 'how effectively your hormones and cells react.'

Insulin Resistance and Fat Metabolism

Many people have wondered about the relationship between insulin resistance and fat metabolism.

The answer lies in two primary players: adipose tissue and free fatty acids. Adipose tissue – or what we lovingly call 'fat' – has a more significant role than simply storing excess energy.

The Role of Adipose Tissue

Studies show that adipose tissue secretes various substances known as adipokines which regulate metabolic processes like glucose uptake and inflammation. Your body's "fluff" isn't just idle; it’s hustling behind the scenes.

A problem arises with too much fat and excessive adiposity (obesity). With obesity comes altered production of these regulating substances leading to impaired glucose tolerance, eventually causing insulin resistance.

Free Fatty Acids And Their Effect On Insulin Sensitivity

The next piece of this puzzle is free fatty acids (FFA).

In normal conditions, free fatty acids help maintain blood sugar levels during periods of fasting. But, like a poorly timed practical joke, elevated FFA levels can harm our body's ability to respond to insulin, the key that lets glucose into cells.

When FFA levels stay high for too long, it results in 'lipotoxicity,' which can harm and disrupt different tissues. This puts us on a slippery slope.

Insulin Resistance and Floaters in the Eyes

Insulin resistance can have far-reaching effects on our health and may even be linked to eye-related issues such as floaters.

While the direct connection between insulin resistance and floaters isn't entirely clear, maintaining a healthy lifestyle, which includes a nutritious diet and regular exercise, is essential for managing insulin resistance.

This approach can contribute to overall eye health. When it comes to addressing how to reduce floaters in eyes naturally, it's recommended to consult with an eye care specialist who can provide specific guidance and treatments tailored to your individual needs.


Understanding insulin resistance and gluconeogenesis is crucial for maintaining optimal health, yet these concepts remain relatively unfamiliar to many. Insulin plays a vital role in regulating blood sugar levels, but issues like insulin resistance can lead to complications such as high blood sugar and eventually type 2 diabetes.

Gluconeogenesis, the process of producing glucose from non-carbohydrate sources, further complicates matters, especially in individuals with insulin resistance or diabetes.

Balancing dietary intake, managing hormone levels, and promoting insulin sensitivity are key strategies in preventing and managing insulin resistance and related health issues.

By adopting a holistic approach to health, including proper nutrition, regular exercise, and medical supervision, individuals can work towards achieving optimal insulin sensitivity and overall well-being.

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