Insulin Resistance and Gluconeogenesis

author avatar Dr. Eric Berg 09/16/2023

Ever wondered why our bodies sometimes seem to rebel against us? Let's dive into the world of insulin resistance and gluconeogenesis explained.

Picture your body as a bustling city, with insulin acting like traffic cops, guiding glucose – the city’s fuel - to where it needs to go. But what happens when these cops start ignoring some cars?

This is akin to insulin resistance. And when you think there's enough chaos, gluconeogenesis kicks in — like factories working overtime, pumping out more fuel.

In this journey through our metabolic metropolis, we'll explore how these processes interact and affect our health.

By reading on, you'll discover why cutting carbs might not consistently lower blood sugar levels or how fat metabolism ties into all this! Ready for an exciting ride through your internal cityscape?

Insulin plays a crucial role in regulating our blood glucose levels. When we eat, the pancreas releases insulin to help cells take up glucose from the bloodstream and use it for energy. But what happens when this system doesn't work as expected?

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 - 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.

A key stat:

  • In people with type 2 diabetes, their livers do not respond appropriately to insulin resulting 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.

It's like a backup generator kicking into steady blood sugar levels. The liver employs gluconeogenic enzymes, like PEPCK, to sustain blood sugar levels when a person is fasting or has low carbohydrate intake.

Hepatic Gluconeogenesis and Insulin Resistance

Don't forget about the role of hepatic insulin.

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 towards insulin to drop dramatically - they start ignoring its calls.

Imagine your neighbor throws a party every night; at first, you're annoyed and lose sleep, but after several weeks or months (depending on your tolerance), you begin sleeping through their raucous laughter and loud music because you've grown accustomed (or resistant) – much like how cells react under constant bombardment of extra insulin due them dealing with uncontrolled blood sugar caused by unhealthy eating habits.

Pancreas Exhaustion: A Precursor to Diabetes Mellitus?

Think of it like running a marathon. At first, you're full of energy and strength. But as the race goes on, fatigue eventually kicks in, just like our pancreas with escalating insulin resistance.

Poor Liver Response to Insulin

Impact 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 - usually associated with lower blood sugars - 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. It's about finding that sweet spot.

Here's the scoop on critical figures: Roughly 5% of folks 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 where our friend 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.' What follows next might sound like an episode from ‘Stranger Things,’ so buckle up.

The Enigma: 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? Well, not quite...

  • 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.

This active endocrine organ releases hormones, cytokines, and, notably, for our discussion - free fatty acids.

The interplay between these components paints an intriguing picture of the link between insulin resistance and fat metabolism. So let's roll up our sleeves (metaphorically).

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 fluff 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 (FFAs). Our friend mentioned earlier primarily releases adipose tissues, pivotal in cellular functions such as membrane synthesis.

In normal conditions, FFAs 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.


Insulin resistance, think of it as traffic cops ignoring cars. It's a big deal in your body’s metabolic city. Gluconeogenesis? That's like factories working overtime, pumping out more fuel than necessary.

Remember the paradox we discussed: cutting carbs doesn't always lower blood sugar levels due to gluconeogenesis kicking into overdrive. Keep this in mind when making dietary choices!

The pancreas tries its best by producing more insulin but sometimes worsens insulin resistance — leading us towards pre-diabetes and diabetes mellitus.

In understanding "Insulin Resistance and Gluconeogenesis Explained," remember how fat metabolism plays its part too. With all these interconnected processes at play, caring for our health becomes an exciting journey through our internal cityscape! Let's navigate wisely for better health outcomes!

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