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Sugar, stress & insulin resistance – what really happens at the cellular level
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Table of contents
- What does insulin resistance mean?
- Why stable blood sugar regulation is more important today than ever
- Effect of insulin: physiological signaling pathway in the cell
- What happens at the cellular level in insulin resistance
- Detecting insulin resistance – why it remains hidden for so long
- Key influencing factors: Excess & mitochondria, inflammation, intestinal barrier & endotoxins, stress & cortisol
- The cell membrane – interface between nutrition and signaling
- Sugar-free, ketogenic & clean diets – what they have in common
- Less sugar, more energy – how nutrition and exercise relieve the burden on your cells
- When blood sugar levels still appear "normal"
- The HOMA index – an early warning system for impaired insulin action
- When blood sugar levels appear normal – why cortisol can complicate early diagnosis
- Mitochondrial boosters & nutrients
- Liver health & insulin resistance
- What can support metabolism in everyday life
- Sleep, micronutrients and stress balance – what your cells really need
- Understanding insulin resistance means thinking about systems together.
Table of contents
- What does insulin resistance mean?
- Stable blood sugar regulation
- Effects of insulin: physiological signaling pathway
- Insulin resistance at the cellular level
- Detecting insulin resistance
- Key influencing factors
- The cell membrane: Nutrition & signaling function
- Sugar-free, ketogenic & clean diet
- Less sugar, more energy: Nutrition & exercise
- Blood sugar levels & effect
- The HOMA index
- Blood sugar & Cortisol
- Mitochondrial boosters & nutrients
- Liver health & insulin resistance
- Supporting metabolism in everyday life
- Sleep, micronutrients and stress balance
- Insulin resistance as a system
Table of contents
- Definition: What is willpower?
- Why willpower is important for achieving goals
- How are willpower and motivation related?
- Why New Year's resolutions so often fail
- The biology behind your energy
- What impairs willpower?
- Why stress acts like poison
- Body, mind & systems: How to strengthen your willpower
- Nutrients as silent partners
- Perseverance beats willpower: Systems as the foundation for discipline
- Systems: 7 tips for more willpower
- The real prize: A body that keeps pace.
- Sources & Bibliography
Introduction
Insulin resistance occurs when cells in muscles, fat, and the liver respond poorly to insulin and can no longer readily absorb glucose from the blood. This means that insulin can no longer adequately perform its function of transporting sugar from the blood into the cells. This physiological mechanism plays a central role in the development of diseases such as type 2 diabetes and metabolic syndrome. For many affected individuals, this has a noticeable impact on their quality of life, as not only is blood sugar metabolism disrupted, but cellular energy supply and related processes such as digestion and nutrient absorption can also be impaired.
What does insulin resistance mean?
Insulin resistance, broadly speaking, means that your cells are no longer as receptive to insulin. Normally, insulin ensures that sugar moves from the blood into the cells, where it is used for energy. If this mechanism is disrupted, the sugar remains in the blood instead of entering the cells – and the body produces more and more insulin to counteract this. This silent process can continue for years before it manifests as a diagnosis such as type 2 diabetes or metabolic syndrome.
The insidious thing is that the causes are often gradual – too little exercise, too many snacks, chronic stress, or a diet that overburdens the mitochondria. People at increased risk should pay particular attention to early warning signs, as timely detection can be crucial . Taking early action can make a big difference – because insulin resistance begins at the cellular level, not just in blood sugar levels.
Why stable blood sugar regulation is more important today than ever
These days, we constantly consume carbohydrates – whether through breakfast, a quick lunch, or a snack in between. Add to that chronic stress, lack of sleep, and insufficient exercise. These factors drive blood sugar spikes and a sustained release of insulin. People who are overweight or sedentary are at particularly high risk of developing insulin resistance – prevention is especially important for them. The consequences are fatigue, cravings for sweets, and often, in the long term, weight gain. When the body repeatedly has too much sugar in the blood, the pancreas constantly releases insulin. Eventually, the muscle or fat cells no longer respond sensitively to it; this is known as insulin resistance . Being overweight, especially with a high proportion of abdominal fat, is considered a crucial risk factor for developing insulin resistance. The main causes of insulin resistance are being overweight, lack of exercise, and an unhealthy diet. Additionally, a genetic predisposition can promote the development of insulin resistance.
Insulin resistance is a key factor in the development of type 2 diabetes and metabolic syndrome. Therefore, keeping blood sugar levels stable and relieving the burden on cells is more important than ever. This shifts the focus from purely blood glucose measurements to a cellular perspective : how insulin resistant are the body's cells really?
How does insulin normally work?
Insulin is a hormone produced by the pancreas that plays a central role in energy metabolism . It acts like a key: it binds to receptors on cell surfaces (such as in muscle or fat cells), thereby triggering a chain of signals. Once insulin docks onto the receptor, an insulin receptor substrate (IRS-1) is activated. This mediator then activates the enzyme PI3K (phosphoinositide 3-kinase) and subsequently the protein kinase Akt (PKB).¹ This cascade causes glucose transporters (GLUT4) to be moved to the cell surface, enabling the cell to take up glucose from the blood . Insulin thus ensures that sugar is transported from the blood into the cells and that blood glucose levels remain stable. If this signaling pathway functions smoothly, insulin transports glucose from the blood into the cells, thereby regulating blood glucose levels in the circulatory system. Insulin resistance occurs when cells in muscles, fat, and liver respond poorly to insulin and can no longer effectively absorb glucose from the blood. When this signaling pathway functions smoothly, blood sugar levels drop normally.
The physiological signaling pathway in the cell
- The insulin receptor binds insulin and triggers molecular mechanisms that are crucial for the action of insulin.
- IRS-1 is phosphorylated (upon tyrosine) and activated (signaling that insulin is present).¹
- The PI3K-ACT pathway is activated, increasing glucose uptake and promoting fat storage in cells.¹
- GLUT4 transporters migrate to the cell membrane and allow sugar (glucose) to enter the cell.
This signaling pathway ensures that excess sugar is cleanly transported from the bloodstream into the cells after a meal.
What happens at the cellular level in insulin resistance
When cells become insulin resistant, this signaling pathway is blocked or weakened. While insulin receptors can still bind insulin, its transmission within the cell is no longer optimal. Often, IRS-1 is dysregulated (e.g., phosphorylated to serine instead of tyrosine), so Akt is not properly activated. Consequently, GLUT4 remains hidden inside the cells, and glucose remains in the bloodstream . Although the pancreas continues to diligently produce insulin, the signal no longer gets through—insulin production is initially even increased to compensate for the elevated blood glucose, until the cells become exhausted. Various organs, such as the liver, muscles, and adipose tissue, are involved in the development of insulin resistance, with visceral fat surrounding these organs playing a particularly significant role. The precise mechanisms of insulin resistance are the subject of ongoing research, but something indeterminate about the interplay of genetics, lifestyle, and metabolic changes is at play. Insulin resistance is part of the metabolic syndrome – a syndrome that combines various risk factors such as high blood pressure, elevated blood lipids, and obesity. The significance of insulin resistance lies in its role as a key factor in the development of type 2 diabetes (diabetes mellitus type 2) and other conditions such as non-alcoholic fatty liver disease (NAFLD).
Detecting insulin resistance – why it remains hidden for so long
The symptoms of insulin resistance are often nonspecific or absent altogether, making early detection difficult. In the long term, insulin resistance can lead to serious health complications such as high blood pressure, heart attack, stroke, and NAFLD. It frequently remains undetected for years and is a major driver of type 2 diabetes and metabolic syndrome. Good blood circulation and healthy blood vessels are crucial for supporting insulin and glucose utilization in the body and preventing secondary diseases. Diagnosis involves measuring blood glucose levels in mmol/L or mg/dL; elevated levels indicate insulin resistance or diabetes mellitus. Insulin resistance is a contributing factor to the development of prediabetes and type 2 diabetes. The development of insulin resistance is complex and involves aspects that are not yet fully understood, which is why it continues to be the subject of intensive research.
Why cells “no longer listen” – key influencing factors
The development of insulin resistance is complex and multifactorial. Among the most important causes are various influencing factors at the cellular level:
Energy surplus & mitochondria
Chronic overconsumption of carbohydrates and fats overloads the cell's powerhouses. The mitochondria then produce increased amounts of reactive oxygen species (ROS) and oxidative stress. These molecules can disrupt insulin signaling.
Experiments show that when too many fatty acids are burned, ROS levels in the muscles rise, which inhibits the insulin cascade.² In the long term, energy production becomes inefficient and the cell switches to a defensive state in which it responds less well to insulin.
inflammation
Chronic inflammatory messengers (cytokines) from excess adipose tissue or stress block the insulin signal.¹ They activate certain kinases (e.g., IKKβ, JNK) that "pin down" IRS-1 (serine phosphorylation), thus stifling the insulin message.¹ In short: inflammatory factors can desensitize insulin receptors.
Fat overload & lipotoxicity
When too much fat is consumed, breakdown products such as diacylglycerides (DAGs) and ceramides accumulate in the cells. These lipids activate protein kinases (e.g., PKCε), which bind directly to the insulin receptor and reduce its activity.³ Studies show that elevated fatty acids in muscle cells lower insulin sensitivity because enzymes like PKCθ inhibit the signaling pathway.¹ Ceramides, in particular, contribute to inflammatory responses and block PI3K action.² The result: Even with high insulin levels, the cell does not open its glucose doors.
Intestinal barrier & endotoxins
A compromised intestinal wall allows bacterial LPS (lipopolysaccharide) to enter the bloodstream—a phenomenon often triggered by an unhealthy diet and stress. LPS binds to Toll-like receptors (TLR4) on immune and liver cells, triggering an inflammatory cascade. This inflammation, in turn, impairs insulin action.⁴ Metabolic endotoxemia (chronically elevated LPS levels) promotes insulin resistance and weight gain.
Stress, Cortisol & Blood Sugar
Under chronic stress and persistent sleep deprivation , the stress hormone cortisol rises chronically. In acute cases, cortisol causes high blood sugar as a "fight-or-flight" energy source. However, in the long term, cortisol antagonizes the effects of insulin and promotes blood sugar spikes. Other stressors (adrenaline, growth hormone) also increase blood sugar levels. Thus, chronic stress can weaken the effect of insulin and promote insulin resistance.
In summary, with insulin resistance, all important systems – energy balance, inflammation, lipid metabolism, gut health, and stress response – are in flux and block each other. There is rarely a single trigger; it is usually a combination of factors.
The cell membrane – interface between nutrition and signaling
Insulin action is influenced not only inside the cell, but also at its surface: The cell membrane contains many fatty acid building blocks that we ingest with our food. Their composition determines membrane fluidity (mobility). A soft, flexible membrane mosaic allows hormone receptors to vibrate more freely and transmit signals more efficiently. Insulin receptors function optimally when the membrane is elastic.⁶
Omega-3 vs. Trans Fats: When distinguishing between monounsaturated and polyunsaturated fats (e.g., omega-3 from salmon, flaxseed oil) and saturated/trans fats (e.g., margarine, French fries), it becomes clear: Omega-3 fatty acids make the cell membrane more fluid.⁶ This enhances the effect of insulin. Trans fats, on the other hand, "glue" the membrane together and block hormone receptors. Studies suggest that trans fats can even reduce insulin sensitivity (especially in tissues already compromised).⁷ In short: Omega-3 strengthens, trans fats weaken.
Polyunsaturated fats (especially omega-3) support healthy cell metabolism. They are incorporated into the cell membrane and increase its fluidity.⁶ This allows insulin to bind more easily to the receptor and transmit its signal.
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Sugar-free, ketogenic and clean diets – what they have in common
All dietary approaches that minimize processed carbohydrates have a beneficial effect on blood sugar and cellular metabolism. Practical nutritional tips for improving insulin sensitivity include avoiding sugar , favoring fiber-rich foods, and regularly consuming vegetables and whole grains. A targeted dietary change with less sugar and more fiber can significantly improve insulin sensitivity. Specific oat days, rich in beta-glucan, can make cells more receptive to insulin. A protein-rich diet also supports weight loss and helps stabilize blood sugar levels. Examples include ketogenic, low-carb, or "clean eating" diets. These are characterized by their ability to keep blood sugar levels stable : Without a strong carbohydrate stimulus, insulin spikes decrease. Studies show that low-carb/keto diets regularly produce effects such as lower fasting insulin levels and reduced HOMA-IR values (a measure of insulin resistance).⁸ This relieves the burden on the liver: Less sugar means less new fat production in the liver.
Learn in our sugar blog how to reduce sugar in everyday life and what alternatives to classic table sugar are available.
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Less sugar, more energy – how nutrition and exercise relieve the burden on your cells
In animal studies, a keto diet even increased fatty acid oxidation in the liver and lowered markers for gluconeogenesis (new glucose production)⁹. In muscles, the mitochondria adapt: Depending on the study, a ketogenic diet increases mitochondrial efficiency and the number of these " cellular powerhouses "⁹. In a study with athletes and healthy subjects, keto, combined with exercise, improved muscle fat metabolism and lowered insulin levels.⁸ In short: Reducing carbohydrate intake stabilizes blood sugar and relieves the burden on the liver and mitochondria (less oxidative stress due to less sugar ). The combination of targeted dietary changes, regular exercise, and weight loss is particularly crucial for preventing or treating insulin resistance.
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When blood sugar levels still appear "normal"
Often, blood glucose levels – both fasting and postprandial – and even the long-term HbA1c value remain within the normal range, although malfunctions are already occurring in the system. Therefore, diagnosing insulin resistance is particularly important to detect changes early and counteract them effectively. This happens because the pancreas produces more insulin until it becomes fatigued. A blood test then shows normal glucose levels, but also indicates hidden stress. Hyperinsulinemia or persistent food cravings are important indicators: In one study, over 30% of healthy young participants already had elevated insulin levels with normal HbA1c. In this study, 10–40% of the subjects had high insulin levels (fasting >15 mIU/L) and thus a significantly increased risk, even before their glucose levels became abnormal.¹³ This shows that chronically elevated insulin levels can rise years before the onset of diabetes.
The HOMA index – an early warning system for impaired insulin action
A key index for diagnosing insulin resistance is the HOMA index. The HOMA index is calculated from fasting insulin (mIU/L) and fasting blood glucose (mg/dL or mmol/L) values using the following formula: (Fasting insulin x Fasting blood glucose) / 405 (for mg/dL) or / 22.5 (for mmol/L). A HOMA index value above 2.0 indicates insulin resistance. The HOMA index is a simple, cost-effective method frequently used in clinical practice to assess glucose metabolism. Precise determination of insulin action, for example using the clamp technique, is complex and is usually only performed in specialized diabetes centers. Elevated levels of intact proinsulin in the blood can also indicate insulin resistance. Early diagnosis of insulin resistance improves the prognosis and can prevent serious complications.
When blood sugar levels appear normal – why cortisol can complicate early diagnosis
Cortisol can also confuse blood glucose levels: In the morning, high cortisol can temporarily raise blood sugar, resulting in normal blood sugar levels but putting a strain on the insulin system. Therefore, it's worthwhile to monitor insulin and cortisol levels early in the process, even if blood sugar appears to be within the normal range. Analyzing data from blood glucose sensors can help provide personalized recommendations for maintaining stable blood sugar and monitoring the progression of diabetes. Important note: This is not a recommendation for self-diagnosis . Medical advice is essential – however, it's important to remember that impaired regulation often only becomes apparent behind seemingly normal blood test results.¹³
Mitochondrial boosters & nutrients
Certain micronutrients can support your mitochondria —and thus your cellular energy and insulin sensitivity. Coenzyme Q10 (CoQ10) is a key element of the mitochondrial electron transport chain. A deficiency in mitochondrial CoQ10 leads to oxidative stress and insulin resistance, while CoQ10 supplementation can restore insulin sensitivity.¹⁵ B vitamins also act as essential coenzymes in energy metabolism: For example, FAD and NAD from vitamins B2 (riboflavin) and B3 (niacin) are required for the respiratory chain.¹⁴ Finally, L-carnitine transports fatty acids into the mitochondria for combustion. Studies show that carnitine supplementation improves mitochondrial function and glucose tolerance.¹⁶
Liver health & insulin resistance
A healthy liver plays a key role in your health, as it regulates sugar and fat metabolism. In fatty liver disease (NAFLD), excess fatty acids accumulate in the liver cells, which is strongly associated with insulin resistance.¹⁷¹⁸ At the same time, the "fatty" liver produces more glucose and VLDL (fat-like particles), which increases the risk of type 2 diabetes and cardiovascular disease.¹⁸ NAFLD is considered the hepatic component of metabolic syndrome and increases the risk of diabetes and cardiovascular disease . Furthermore, in fatty liver disease, the liver's detoxification and fat-breakdown functions decrease—a vicious cycle that puts additional strain on your metabolism.¹⁸
What can support metabolism in everyday life
Many everyday activities sensitize insulin. A diet should consist of plenty of whole grains, vegetables, fruits, nuts, and high-quality fats (e.g., olive oil, flaxseed oil). The combination of lifestyle changes and, if necessary, medication is crucial for overcoming insulin resistance. Regular exercise (endurance and strength training) is extremely helpful: just 30 minutes of strength training several times a week significantly increases insulin sensitivity in the muscles.¹⁰ This occurs, among other things, through increased GLUT4 transporters and improved blood flow to the muscles. In certain cases, a doctor may prescribe medications such as glitazones, but these do not replace lifestyle changes. Drinking diluted apple cider vinegar before meals can also lower blood sugar levels after eating.
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Sleep, micronutrients and stress balance – what your cells really need
Sufficient sleep (7–9 hours) is also important. Chronic sleep deprivation increases stress hormones and inflammatory markers , which in turn reduces insulin sensitivity. Stress management (e.g., yoga, mindfulness) can mitigate cortisol spikes. Micronutrients also support a healthy metabolism: Omega-3 fatty acids have anti-inflammatory effects (see above)⁶. Vitamin D plays a role: It directly promotes insulin sensitivity and cellular ownership of anti-inflammatory cytokines.¹² Magnesium is a cofactor in energy and insulin metabolism; a deficiency disrupts mitochondrial function . Studies in mice showed that magnesium supplementation improves mitochondrial performance (more ATP, fewer ROS) and could have a supportive effect.¹¹ It is important not to supplement arbitrarily, but rather to strive for a balanced nutritional and micronutrient status in consultation with experts. When formulating recommendations, it is important to remember that all these measures can be supportive and can contribute to the normal function of metabolism, the inflammatory response, the nervous system, and cell protection. They are not a "miracle solution", but together they can help considerably.
Understanding insulin resistance means thinking about systems together.
Insulin resistance is often reduced to blood glucose processes, but it can also be viewed within the context of diverse metabolic relationships. A systemic understanding focuses on different metabolic pathways and their interactions. These include processes in the gut (e.g., barrier function and microbiome), in the mitochondria (energy metabolism, redox processes), at the cell membrane (fatty acid composition), and in the hormonal system (e.g., insulin, cortisol, adipokines). From this perspective, a holistic picture emerges, clarifying that, in addition to diet, factors such as stress and the quality of dietary fats are also considered influencing factors.
Conclusion
Insulin resistance is described in the scientific literature as a multifactorial phenomenon that cannot be attributed to a single influencing factor. It is frequently discussed in connection with metabolic syndrome, a cluster of metabolic abnormalities. In this context, a holistic view of lifestyle factors such as diet, exercise, sleep, stress, gut function, and eating patterns is considered a helpful perspective for better understanding complex metabolic processes.
From this perspective, it follows that lifestyle factors can act simultaneously on different levels and influence the metabolic adaptability of cells.
Insulin resistance is also described as a physiological adaptation phenomenon during pregnancy, associated with hormonal changes. This temporary adaptation is closely monitored in medical practice because it has its own distinct significance in the context of pregnancy.
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This article is based on carefully researched sources:
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