Inside your cells: mitochondria, ATP, and insulin

TL;DR. Every cell needs ATP. Mitochondria make it from food. Insulin tells cells where to store extra fuel. Modern food overwhelms this system. The result is "metabolic dysfunction," and it sits upstream of type 2 diabetes, fatty liver, PCOS, atherosclerosis, and Alzheimer's. Casey Means cites a UNC study: 93.2 percent of U.S. adults are metabolically unhealthy. Once you see the machinery, you see why the same fixes work for very different diseases. Less sugar, less seed oil, more fiber, more real food. They all take pressure off the same engine.

What you'll learn

• What ATP is and why every cell needs it.
• How your mitochondria turn food into ATP. What "Bad Energy" looks like inside one cell.
• What insulin does. Why it matters more than glucose. How it flips your body between storage and burn.
• Why insulin resistance shows up years before any standard lab catches it.
• Lustig's 8 cellular pathologies and why food fixes what drugs can't.
• Why fructose is a special case.
• 3 levers that take pressure off the system.

The energy hierarchy: food becomes ATP becomes everything

You have about 37 trillion cells. Each one runs on a rechargeable molecule called adenosine triphosphate, or ATP. You don't store ATP. The average adult makes and burns about 88 pounds of it a day. ATP runs protein building, DNA repair, ion pumps, muscle contraction, nerve signals, immune defense, and autophagy (your cell's cleanup crew). When ATP runs short, work stalls. The cell signals for help. Over time, tissues stop doing their jobs.

Your mitochondria make almost all of your ATP. These are small parts inside almost every cell. They came from a free-living bacterium that got swallowed by a larger cell about 1.5 billion years ago. Each cell holds hundreds to thousands of mitochondria. The hungriest tissues hold the most: heart muscle (about 5,000 per cell), skeletal muscle, kidney, liver, and brain. An egg at ovulation carries hundreds of thousands. "Metabolically active tissue" means "mitochondria-rich tissue."

The chemistry is long. The point is short. Your body breaks carbs, fats, and protein down to one molecule called acetyl-CoA. Acetyl-CoA feeds the Krebs cycle inside your mitochondria. The Krebs cycle pulls electrons off acetyl-CoA and loads them onto two carriers (NADH and FADH2). Those carriers drop the electrons down the electron transport chain. The energy from that drop pumps protons across a membrane. The protons flow back through an enzyme called ATP synthase. That enzyme spins like a tiny turbine and welds a phosphate onto ADP. You get ATP. Oxygen sits at the end of the chain and catches the spent electrons. That is why you breathe.

When mitochondria get damaged or buried in fuel, the whole line stalls. Pyruvic acid backs up, leaves the mitochondria, and your liver turns it into fat (de novo lipogenesis). Electrons leak off the chain and form reactive oxygen species. That is "oxidative stress." Cells that can't make enough ATP can't do their jobs, and they signal for help. Casey Means calls the healthy state "Good Energy" and the broken state "Bad Energy." The rest of this module shows how modern food drives cells toward the second one.

Insulin: the storage signal

Insulin is a small protein hormone. The beta cells of your pancreas make it. It is your body's main fuel-storage signal. When you eat carbs, your blood glucose rises. Your pancreas releases insulin. Insulin tells your cells what to do with the new fuel. Muscle cells take up glucose and burn it or store it as glycogen. Liver cells store glycogen, and if any glucose is left, turn it into triglyceride. Fat cells take up fatty acids and lock them away. Insulin says "store this" and "stop burning fat" at the same time. When insulin is high, fat cells can't release fat for fuel.

Before 1960, no one could measure insulin in human blood. Solomon Berson and Rosalyn Yalow built the radioimmunoassay that year at the Bronx VA. Yalow won the 1977 Nobel Prize for it (Berson had died). Endocrinology became quantitative overnight. The first thing the new test showed: obese people and type 2 diabetics had high glucose and high insulin. Their pancreases were pumping out far more insulin than normal. That changed the question of obesity. Eating raises insulin. High insulin locks fat into fat cells. The older European view of obesity as a hormone problem suddenly had a hormone to measure.

Your body is built to swing between two states. Fed state: you ate, glucose is up, insulin is up, you store and grow. Fasted state: glucose drops, insulin falls, glucagon rises, your liver releases stored glycogen, fat cells release fatty acids, and your liver turns some of those fatty acids into ketones. You burn your own reserves. Both states are normal. The modern pattern is not. Snacks, sweet drinks, and processed carbs from waking to bed keep insulin high all day. Cells stop responding to a signal that never stops, like a doorbell that never quits. The pancreas rings the bell harder.

That is insulin resistance. It is the most important upstream change in modern chronic disease. Fasting glucose can stay "normal" for years while fasting insulin climbs. Eventually the pancreas can't keep up. Glucose drifts up. You get diagnosed with prediabetes, then type 2 diabetes. By then the real problem has been brewing for decades.

Insulin resistance and metabolic syndrome

In 1988, Stanford endocrinologist Gerald Reaven gave the Banting Lecture to the American Diabetes Association. He said something heretical. Obesity, type 2 diabetes, high blood pressure, atherosclerosis, bad cholesterol, and glucose problems were not separate diseases that happened to cluster. They were branches of one upstream defect: insulin resistance and the high insulin that came with it. He called it Syndrome X. The field later renamed it metabolic syndrome.

You meet the current criteria (NCEP ATP III) if you have any 3 of 5: waist over 40 inches in men or 35 in women; fasting triglycerides at or above 150 mg/dL; HDL below 40 in men or 50 in women; blood pressure at or above 130/85; fasting glucose at or above 100 mg/dL. The cluster makes mechanical sense. High insulin tells your kidneys to hold sodium, which raises blood pressure. It tells your liver to make more triglyceride-rich VLDL, which lowers HDL and pushes LDL toward the small, dense, artery-clogging form. It pushes fat into places fat shouldn't live: liver, pancreas, muscle. That is the visible signature of metabolic syndrome.

In 2022, Joana Araújo and colleagues at the University of North Carolina ran NHANES data and found that only 6.8 percent of U.S. adults hit optimal cardiometabolic health on all 5 measures. So 93.2 percent of American adults are metabolically unhealthy. Means treats that number as the central public-health fact of the era. It isn't really contested. It is just buried. Most of those 93 percent have no diagnosis yet. They have rising fasting insulin, rising HOMA-IR (fasting insulin times fasting glucose, divided by 405), and rising triglyceride-to-HDL ratios. None of that shows up at a standard annual physical. Most doctors don't order fasting insulin. The lab's "normal" fasting glucose runs up to 99 mg/dL.

This is why Lustig and Means both push fasting insulin as the single best lab test. By the time HbA1c moves, the machinery has been broken for 10 or 20 years. Insulin resistance starts decades before high blood sugar. Bad Energy is silent.

The 8 cellular pathologies (Lustig's framework)

Robert Lustig is a UCSF pediatric endocrinologist. His 2009 lecture "Sugar: The Bitter Truth" launched the modern anti-sugar argument. In Metabolical, he argues that chronic disease is really 8 cell-level processes going wrong. None has a clean drug target. That is why pharma has spent billions on drugs for fatty liver and Alzheimer's with almost nothing to show for it. All 8 respond to food.

Glycation is the Maillard reaction happening inside you. Sugars stick to proteins without help from any enzyme. They form advanced glycation end products (AGEs) that stiffen tissues, scar arteries, and trigger receptors that drive inflammation. Fructose glycates about 7 times faster than glucose. Its breakdown product methylglyoxal is 250 times faster. Oxidative stress is the leak of reactive oxygen species off the electron transport chain. They overwhelm your cell's defenses: glutathione, superoxide dismutase, catalase, and the Nrf2 response. Mitochondrial dysfunction is your mitochondria themselves getting worse. You have fewer of them, fatter and lazier folds (cristae), and less throughput.

Insulin resistance is the section above. Membrane integrity is what happens when industrial seed oils push fish-based omega-3s out of your cell membranes. The U.S. diet has shifted the omega-6 to omega-3 ratio from about 1:1 in our past to about 20:1 today. Your fat tissue ratio can shift in days when you change your food. Inflammation is low-grade signaling driven by a leaky gut, dietary AGEs, palmitate from new fat your liver builds, and visceral fat acting like a gland.

Epigenetics is the layer of methyl and acetyl marks that turn genes on and off without changing the DNA itself. A mother's food, stress, and toxin load can leave marks that last several generations. Autophagy is your cell's nightly cleanup. It recycles damaged proteins and worn-out mitochondria. Your brain's glymphatic system clears metabolic waste the same way. Fasting, exercise, and certain food compounds trigger autophagy (urolithin A from pomegranate; sulforaphane from broccoli). Constant eating and constant insulin shut it down.

Lustig's point: these pathways sense nutrients. They respond to what you eat, when you eat it, and what your gut bugs do with it. They don't respond well to drugs. Drugs are built to hit single targets. These pathways work together. That is the real reason one move, eat real food instead of industrial stuff, keeps showing up as the answer for diseases that look nothing alike. Type 2 diabetes, fatty liver, PCOS, Alzheimer's, depression, and atherosclerosis all sit on the same upstream axis.

Fructose: the special case

Fructose deserves its own paragraph. It is not the same as glucose. Every cell in your body can use glucose. Your brain alone burns about 120 grams a day. Fructose almost only gets handled by the liver. When a 12-ounce soda hits your gut, the glucose half spreads across the body and gets used. The fructose half lands in your liver in one shot.

Inside the liver, fructose skips the step (phosphofructokinase) that normally slows sugar breakdown when energy is high. With no brake, fructose carbons turn into fat through de novo lipogenesis. That is the same path ethanol uses to build a fatty liver. Lustig's argument is biochemically literal. A steady high-dose fructose load does to the liver what a steady alcohol load does. Fructose runs the Maillard reaction 7 times faster than glucose. Its byproduct methylglyoxal runs 250 times faster. It raises uric acid, which separately hurts mitochondria. It crosses the placenta. It shows up in breast milk in proportion to how much soda the mother drinks.

That is why an apple is fine and a 12-ounce soda is not, even at the same fructose total. The apple delivers fructose slowly, wrapped in fiber, and your gut absorbs it over an hour or more. Your colon bacteria ferment what's left into short-chain fatty acids. The soda delivers fructose fast, with no fiber, in one pure hit to the liver. Children now get adult diseases of alcohol (fatty liver, type 2 diabetes) without ever drinking. Up to 20 percent of U.S. children, and 42 percent of Hispanic men aged 25 to 30, have nonalcoholic fatty liver disease.

What this means for action

If one engine is getting overrun by a small set of inputs, the fixes don't need to be exotic. 3 categories take pressure off the system. They go in rough order of leverage.

First, cut continuous insulin signaling. For most people, the biggest single gain is dropping sugar-sweetened drinks. A can of soda is a pure hepatic fructose hit with nothing to slow it down. The second biggest is shifting your carbs toward whole, fiber-bound forms: beans, whole grains, fruit, vegetables. The third is letting your body see a low-insulin window every day. A 12 to 14 hour overnight gap (last meal 3 hours before bed, breakfast the next morning) gives your liver time to clear fat and gives autophagy room to work. You don't have to be hungry. You just have to stop eating something every 2 hours.

Second, cut oxidative and inflammatory load. Your fat-tissue omega-6 to omega-3 ratio can shift in days. Use fewer refined seed oils (soybean, corn, cottonseed, "vegetable oil"). Eat more cold-water fish or omega-3 eggs. Use more olive oil. Eat more whole-plant antioxidants from real food. The Nrf2 pathway, your cell's master antioxidant switch, gets activated by isothiocyanates in cruciferous vegetables (broccoli, brussels sprouts, arugula) and by polyphenols in berries, tea, and dark chocolate. This isn't supplementation. It is eating plants on a regular schedule.

Third, build mitochondrial capacity. Mitochondria aren't fixed. They grow and shrink based on demand. Zone-2 cardio (brisk walking, easy cycling, anything you can talk through) is the most-studied trigger for new mitochondria. Resistance training builds active tissue that pulls glucose out of your blood without much insulin. That adds buffer for everything else. Sleep helps too. 7 to 9 hours supports the autophagy and glymphatic cleanup your mitochondria need. 6 days of 4-hour sleep can push healthy adults into measurable prediabetes. Cold exposure activates brown fat, which is dense with mitochondria by design.

How you frame it matters. You aren't doing 6 different things. You are taking pressure off one piece of machinery in 3 ways.

Frequently Asked Questions

Does this mean low-carb is the answer?

Low-carb works for many people because it lowers chronic insulin signaling. So does Mediterranean. So does whole-food plant-based. So does time-restricted eating. The shared mechanism is "stop hammering the machinery." It isn't "cut out this macronutrient." Lustig's 6-word version: protect the liver, feed the gut. Several diets do both.

Are insulin sensitivity and insulin resistance opposite ends of a spectrum?

Roughly, yes. Sensitivity means your cells respond strongly to a small amount of insulin. Resistance means they need more and more to do the same job. HOMA-IR is the most common single-number summary. You calculate it from fasting insulin and fasting glucose. Below about 1.0 is excellent. Above 2.5 to 2.8 means real resistance.

Are GLP-1 drugs (Ozempic, Wegovy) treating insulin resistance?

Indirectly. GLP-1 agonists slow stomach emptying, soften glucose spikes after meals, and cut appetite. The weight loss they cause does improve insulin sensitivity. But they don't fix the upstream pathway. They put a chemical brake on intake. Stop the drug, and unless your food has changed, the resistance comes back. That fits the rest of the chronic-disease-drug pattern.

Is fasting good for mitochondria?

Yes, in the mild sense most people mean. A 12 to 14 hour overnight gap, occasional 16-hour windows, or occasional 24-hour fasts trigger autophagy and mitophagy (clearing damaged mitochondria) and let AMP-kinase turn on. Extreme protocols (multi-day fasts, long ketosis) have separate trade-offs and aren't needed for the core benefit.

How is metabolic syndrome different from prediabetes?

Prediabetes is defined by glucose alone (fasting glucose 100 to 125 mg/dL, or HbA1c 5.7 to 6.4 percent). Metabolic syndrome is the broader cluster: waist, blood pressure, triglycerides, HDL, glucose. It catches the same underlying problem earlier and across more tissues. You can have metabolic syndrome with perfectly normal fasting glucose.

Why do thin people get metabolic syndrome?

"TOFI" means thin on the outside, fat on the inside. These people have normal visible body fat. Their visceral fat and liver fat are sick. About 40 percent of normal-weight U.S. adults are metabolically unhealthy. BMI misses them. Waist size, fasting insulin, triglyceride-to-HDL ratio, and ALT catch them.

Why does this matter if I'm not diabetic?

Because metabolic dysfunction sits upstream of most of what eventually kills Americans. Alzheimer's risk roughly doubles in type 2 diabetics. The literature now calls late-onset Alzheimer's "type 3 diabetes." Cardiovascular disease, the leading cause of death in the U.S., tracks insulin resistance better than it tracks LDL cholesterol. PCOS, infertility, NAFLD, gout, and many cancers share the same upstream mechanism. The diagnosis comes late. The machinery breaks early.

Is this the same as the "carnivore diet is the answer" position online?

No. The case here is that the upstream problem is overrun cellular machinery. Real food in several patterns (Mediterranean, whole-food plant-based, traditional low-carb, time-restricted whole-food) gives that machinery room to recover. The carnivore claim that all plants are the problem is not what the biochemistry says.

Sources

1. Means, C. Good Energy: The Surprising Connection Between Metabolism and Limitless Health (2024). The 93.2 percent figure comes from Araújo, J., Cai, J., Stevens, J. "Prevalence of Optimal Metabolic Health in American Adults." Metabolic Syndrome and Related Disorders, 2019. DOI: 10.1089/met.2018.0105.
2. Lustig, R. H. Metabolical: The Lure and the Lies of Processed Food, Nutrition, and Modern Medicine (2021). Eight subcellular pathologies; fructose biochemistry.
3. Taubes, G. The Case Against Sugar (2016). Yalow and Berson 1960 radioimmunoassay; insulin as the dominant lipogenic hormone.
4. Gropper, S. S., Smith, J. L., Carr, T. P. Advanced Nutrition and Human Metabolism, 8th edition (2022). Mitochondrial ATP production; AMPK and mTOR; carnitine shuttle; de novo lipogenesis.
5. Reaven, G. M. "Banting Lecture 1988: Role of insulin resistance in human disease." Diabetes, 1988;37(12):1595–1607. DOI: 10.2337/diab.37.12.1595.
6. Yalow, R. S., Berson, S. A. "Immunoassay of endogenous plasma insulin in man." Journal of Clinical Investigation, 1960;39(7):1157–1175. DOI: 10.1172/JCI104130.
7. Hall, K. D., et al. "Ultra-processed diets cause excess calorie intake and weight gain." Cell Metabolism, 2019;30(1):67–77.e3. DOI: 10.1016/j.cmet.2019.05.008.

Related glossary terms

• Mitochondria
• ATP
• Insulin
• Insulin resistance
• AMPK
• Metabolic syndrome
• Oxidative stress
• Nrf2