CHAPTER 2 — INSULIN RESISTANCE: THE CELLULAR MECHANISM Insulin resistance is the central engine that drives Type 2 Diabetes. To understand how to reverse or improve Type 2 Diabetes, it is essential to understand what happens at the cellular level in the liver, muscles, and fat tissue. OVERVIEW OF INSULIN ACTION After a meal, carbohydrates are broken down into glucose, which enters the bloodstream. Rising blood glucose triggers the pancreas to release insulin. Insulin travels in the blood and attaches to insulin receptors on the surface of cells, mainly in muscle, liver, and fat tissue. When insulin binds to its receptor, a signal is sent inside the cell which leads to:
- Movement of glucose transporters to the cell surface
- Entry of glucose into the cell
- Use or storage of glucose for energy
In a healthy system, this process is smooth and efficient. Insulin rises, glucose enters the cells, and blood sugar returns to a normal range. WHAT GOES WRONG IN INSULIN RESISTANCE In insulin resistance, the receptors and internal signaling pathways become less responsive. The same amount of insulin now produces a weaker effect. The body reacts by producing more insulin and keeping insulin levels high for longer periods. Key changes include: 1. Insulin receptor signaling becomes impaired. 2. Fewer glucose transporters move to the cell membrane. 3. Less glucose enters the cells. 4. Blood sugar remains elevated. 5. The pancreas must produce more insulin to compensate. Over time this can exhaust the beta cells in the pancreas and lead to persistent high glucose. ROLE OF MUSCLE CELLS Skeletal muscle is the largest site of glucose disposal in the body. When muscle cells are sensitive to insulin, they take up a significant portion of post meal glucose and burn it for energy or store it as glycogen. In insulin resistance:
- Fat droplets accumulate inside muscle cells, known as intramyocellular fat.
- These fat deposits interfere with insulin signaling pathways.
- Inflammatory molecules within the muscle environment further block signaling.
- As a result, muscle cells respond poorly to insulin and take up less glucose.
When muscles do not clear glucose effectively, more glucose remains in the blood, and more insulin is required to manage the same meal. ROLE OF THE LIVER The liver acts as a glucose buffer. It stores glucose as glycogen after meals and releases glucose between meals and overnight to keep blood levels stable. Under healthy conditions:
- Insulin tells the liver to stop releasing glucose when levels are high.
- Insulin also promotes storage of glucose as glycogen.
In insulin resistant liver cells:
- The liver does not correctly sense the insulin signal.
- It continues to release glucose into the blood even when glucose is already high.
- The liver may convert excess glucose and fat into triglycerides, contributing to fatty liver.
This combination of extra glucose output and fat accumulation in the liver is a major driver of elevated fasting glucose and abnormal blood tests in Type 2 Diabetes. ROLE OF FAT TISSUE Fat tissue is designed to store energy safely. When storage capacity is healthy and balanced, fat cells can expand and contract without causing metabolic harm. However, when fat cells become overfilled or inflamed:
- They release more free fatty acids into the bloodstream.
- They produce inflammatory cytokines that interfere with insulin signaling in the liver and muscles.
- They become resistant to insulin themselves and do not store fat efficiently.
Excess free fatty acids travel to other organs such as the liver, pancreas, and muscles. This ectopic fat creates lipotoxicity, which damages cells and further reduces insulin sensitivity. LOW GRADE INFLAMMATION Insulin resistance is closely linked to chronic low grade inflammation. Sources of this inflammation include:
- Visceral fat around the organs
- Fatty liver
- Unhealthy gut barrier and microbiome changes
- Processed food intake
- Oxidative stress
Inflammatory molecules disrupt insulin signaling pathways, making it more difficult for insulin to work even when levels are high. This sets up a vicious cycle where inflammation leads to insulin resistance and insulin resistance leads to more inflammation. BETA CELL COMPENSATION AND FATIGUE In the early stages, the pancreas tries to overcome insulin resistance by producing more insulin. This stage is sometimes called compensated insulin resistance. Over years:
- Beta cells are exposed to high glucose and high fat levels.
- This environment is toxic for them, a process known as glucotoxicity and lipotoxicity.
- Beta cells begin to lose function and may die.
- Insulin production declines.
When the pancreas can no longer keep up, blood glucose rises more sharply and Type 2 Diabetes becomes more obvious in blood tests. WHY WEIGHT IS NOT THE ONLY FACTOR Many people with Type 2 Diabetes carry extra weight, especially around the abdomen, but not everyone with insulin resistance is visibly overweight. Factors such as genetics, muscle mass, fat distribution, sleep quality, stress, and diet pattern all influence how sensitive or resistant a person is to insulin. Two people with the same body weight can have very different levels of insulin resistance, depending on where they store fat and how inflamed their tissues are. KEY POINTS SUMMARISED
- Insulin resistance begins at the cellular level in muscles, liver, and fat tissue.
- Intracellular fat and inflammatory molecules block insulin signaling.
- Muscles fail to take up enough glucose.
- The liver continues to release glucose when it should stop.
- Fat tissue leaks fatty acids and inflammatory signals into the system.
- The pancreas compensates by producing more insulin, which over time can lead to beta cell fatigue.
GOOD NEWS Insulin resistance is dynamic and can be improved. Reducing liver and visceral fat, increasing muscle activity, improving sleep, lowering stress, and changing food quality and timing can restore a significant amount of insulin sensitivity. Later chapters will explain how to apply daily strategies to:
- Reduce liver and abdominal fat
- Improve muscle glucose uptake
- Calm inflammation
- Support and protect beta cells
By understanding the cellular mechanism, every lifestyle change becomes more meaningful and targeted, rather than a random list of rules.