Biology: Spier als orgaan

What It Is

Skeletal muscle moves the skeleton, and it is also the body's largest metabolic and endocrine organ. At roughly 40% of body weight, it is the biggest single tissue, and after a meal most of the blood's sugar is pulled into it. How much a person carries, and how well it responds to insulin, sets how the whole body handles food.

How It Works

What muscle does beyond movement

1It is the largest glucose sink

When insulin clears sugar from the blood after a meal, insulin-clamp studies show about 80% of it goes into skeletal muscle. Fat takes a small single-digit share and other tissues take very little. Muscle is a large fraction of body mass, so its insulin sensitivity sets how the whole body handles a meal. Impaired glucose uptake into muscle is the earliest measurable defect in type 2 diabetes.

2It secretes myokines when it contracts

A contracting muscle releases proteins into the blood that act on other tissue. These are called myokines, and their discovery in the early 2000s established muscle as a secretory organ. Working fibers release the best-studied one, interleukin-6 (IL-6), without any damage. During a long bout of exercise IL-6 can climb up to a hundredfold, promoting glucose uptake and fat oxidation as a metabolic messenger. When IL-6 instead stays high at rest for a long time, the same molecule turns pro-inflammatory.

3It signals to fat, bone, liver and brain

Myokines reach distant organs, which is what makes muscle an endocrine tissue. The clearest example runs from muscle to brain. In mice, running raises a muscle protein called cathepsin B. Cathepsin B crosses into the brain, lifts the growth factor BDNF, increases new hippocampal neurons, and improves memory. A small 2016 human sample pointed the same way, but the pathway is still preliminary and rests mostly on animal work.

The three jobs differ in how firmly they are proven. The glucose-sink role is settled. The endocrine role is solid for IL-6 and still being worked out for the other myokines. Irisin, announced in 2012, is the least settled of all.

Irisin was billed as an exercise hormone that turns white fat into calorie-burning brown-like fat, and the claim spread fast before drawing skepticism from other labs. Some antibodies used to measure it bound the wrong proteins, and a few researchers doubted human irisin existed at all. Later mass-spectrometry work showed it does circulate in people, at low levels near 3.6 ng/ml that rise to about 4.3 ng/ml with training. Whether that rise means anything is unsettled, and much of the popular claim still rests on mouse data and early tests that did not replicate.

What It Does

Grip strength forecasts how long a person lives. In the PURE study, Leong 2015 followed 139,691 adults across 17 countries. Each 11 lb (5 kg) drop in grip predicted a 16% higher risk of death over the next four years. The link is observational: grip marks whole-body muscle, and weak hands often signal an illness already under way. A dynamometer reading is cheap to take and hard to inflate on purpose. See grip strength for how it is measured.

The Research & Studies

Everything here is based on the research we have collected and checked, sorted into groups and ordered with the strongest evidence first. Click any claim to open the studies behind it.

How it works

Muscle takes up about 80% of the glucose insulin clearsStrong

In plain terms

After a meal, most of the sugar that leaves your blood is pulled into muscle. Skeletal muscle takes up about 80% of the glucose that insulin moves, which makes it the body's main sugar sink.

In detail

Euglycemic-hyperinsulinemic clamp studies established skeletal muscle as the principal site of insulin-mediated glucose disposal, taking up on the order of 80% under insulin stimulation, and identified impaired muscle glucose uptake as the earliest and primary defect in type 2 diabetes. Because muscle is such a large fraction of body mass, its insulin sensitivity dominates whole-body glucose handling.

The study · 1

DeFronzo & Tripathy, skeletal muscle insulin resistance is the primary defect in type 2 diabetes · Diabetes Care 2009;32 Suppl 2:S157-63

Resting muscle burns about 13 kcal per kg per dayStrong · mixed

In plain terms

At rest, a kilogram of muscle burns only about 13 calories a day, a few times more than fat but far less than the liver or brain. Gaining a few kilograms of muscle raises resting calorie burn by a modest amount, not the large figure often quoted.

In detail

Elia's classic organ metabolic rates put skeletal muscle at about 13 kcal/kg/day. Wang and colleagues validated those values across adulthood using whole-body resting energy expenditure by indirect calorimetry with organ and tissue masses measured by magnetic resonance imaging in 131 non-obese healthy adults, with age-adjusted muscle values near 12.6 kcal/kg/day in those over 50. Because muscle is a large fraction of body mass it still contributes a sizeable slice of total resting expenditure, but the per-kilogram rate is low, so the claim that gaining muscle greatly raises the metabolism overstates the effect.

Who this may not transfer to:Modelled in non-obese healthy adults; the per-kilogram rate is a tissue property expected to hold broadly, though a person's total contribution scales with how much muscle they carry.

The study · 1

Wang et al., specific metabolic rates of major organs and tissues across adulthood, evaluation by mechanistic model of resting energy expenditure · Am J Clin Nutr 2010;92(6):1369-77

Contracting muscle releases IL-6, rising up to about 100-foldModerate

In plain terms

When muscle contracts, it releases hormone-like proteins into the bloodstream. The clearest example is IL-6, which can climb up to a hundredfold during a long bout of exercise and signals to other organs, behaving as a messenger, not a sign of injury.

In detail

Pedersen and Febbraio's work reframed muscle as a secretory (endocrine) organ. IL-6 is produced by contracting fibers independent of muscle damage; its release scales with exercise intensity, duration and low muscle glycogen, and in the exercise context it promotes glucose uptake and fat oxidation and drives anti-inflammatory cascades, in contrast to the pro-inflammatory role of chronically elevated resting IL-6. A growing list of other candidate myokines has since been catalogued.

The studies · 2

Pedersen & Febbraio, muscle as an endocrine organ, focus on muscle-derived interleukin-6 · Physiol Rev 2008;88(4):1379-406

Pedersen & Febbraio, muscles, exercise and obesity, skeletal muscle as a secretory organ · Nat Rev Endocrinol 2012;8(8):457-65

Building older muscle took 0.40 g protein per kg per meal, versus 0.24 in the youngModerate · mixed

In plain terms

Older muscle responds less readily to protein. To fully switch on muscle building, older men in these studies needed roughly 0.40 g of protein per kg of body weight in a meal, versus about 0.24 g/kg for young men, so the older body needs a bigger protein dose for the same signal.

In detail

Moore and colleagues retrospectively pooled myofibrillar protein synthesis data measured by primed constant L-[13C6]phenylalanine infusion after boluses of 0-40 g high-quality protein. Basal synthesis did not differ by age, but biphasic breakpoint analysis showed the per-meal protein needed to plateau synthesis was higher in older men (0.40 vs 0.24 g/kg body mass; 0.60 vs 0.25 g/kg lean body mass). This anabolic resistance is a leading reason muscle is harder to hold in later life.

Who this may not transfer to:Measured in men only; the per-meal protein threshold for maximal muscle protein synthesis in women has not been established the same way, so the exact figures should not be assumed identical.

The study · 1

Moore et al., protein ingestion to stimulate myofibrillar protein synthesis requires greater relative protein intakes in older versus younger men · J Gerontol A Biol Sci Med Sci 2015;70(1):57-62

Irisin circulates in people, its fat-browning role unsettledEmerging · mixed

In plain terms

Irisin is a much-hyped 'exercise hormone' said to turn ordinary fat into calorie-burning fat. The picture is unsettled: early antibody tests were unreliable and some researchers doubted it existed in people, though careful mass-spectrometry work later showed it does circulate, at low levels that rise a little with exercise.

In detail

The 2012 discovery paper described irisin as a PGC1-alpha-dependent myokine that drives brown-fat-like development of white adipose tissue in mice. The claim drew heavy scrutiny: a 2015 analysis argued the commercial ELISA antibodies were non-specific and questioned whether human irisin was real, while a 2015 tandem mass spectrometry study detected and quantified circulating human irisin and found it rose with exercise. The metabolic significance of those low circulating levels in humans is not established.

The studies · 3

Bostrom et al., a PGC1-alpha-dependent myokine that drives brown-fat-like development of white fat (irisin discovery) · Nature 2012;481(7382):463-8

Albrecht et al., irisin, a myth rather than an exercise-inducible myokine · Sci Rep 2015;5:8889

Jedrychowski et al., detection and quantitation of circulating human irisin by tandem mass spectrometry · Cell Metab 2015;22(4):734-40

In mice, muscle-made cathepsin B lifts brain BDNF and memoryPreliminary

In plain terms

Exercising muscle may talk to the brain. In mice, running raises a muscle protein called cathepsin B that increases a growth factor (BDNF) and new hippocampal neurons, improving memory. A small human study found the same protein rose with fitness and tracked with memory, which is an early hint.

In detail

Moon and colleagues showed running increased cathepsin B in mouse muscle and plasma; recombinant cathepsin B raised BDNF and doublecortin in adult hippocampal progenitors, and cathepsin B knockout mice failed to gain neurogenesis and spatial memory from running. In a small cohort of healthy adults, treadmill-associated changes in cathepsin B correlated with fitness and memory. It is one strand of a broader muscle-organ crosstalk literature reviewed as the myokine field expanded.

The studies · 2

Moon et al., running-induced systemic cathepsin B secretion is associated with memory function · Cell Metab 2016;24(2):332-40

Severinsen & Pedersen, muscle-organ crosstalk, the emerging roles of myokines · Endocr Rev 2020;41(4):594-609

Blood Sugar

Each 10% more relative muscle mass, 11% lower insulin resistanceModerate

In plain terms

People carrying more muscle for their body size tend to handle blood sugar better. In a large US survey, each 10% more relative muscle mass came with about 11% lower insulin resistance and 12% less prediabetes.

In detail

Srikanthan and Karlamangla analyzed NHANES III (n=13,644), estimating skeletal muscle index by bioelectrical impedance as muscle mass relative to body weight. Across the full range, higher relative muscle mass was associated with lower HOMA-IR (11% relative reduction per 10% higher index, 95% CI 6-15%) and lower prevalence of prediabetes (12% relative reduction, 95% CI 1-21%), with associations stronger in non-diabetics, after adjustment for age, ethnicity, sex and generalized and central obesity.

The study · 1

Srikanthan & Karlamangla, relative muscle mass is inversely associated with insulin resistance and prediabetes (NHANES III) · J Clin Endocrinol Metab 2011;96(9):2898-903

Progress Markers

Each 11 lb (5 kg) weaker grip, 16% higher risk of deathModerate

In plain terms

How hard you can squeeze is a surprisingly strong marker of health. In a study of nearly 140,000 people, every 11 lb (5 kg) less grip strength went with a 16% higher risk of dying over the next few years, a better predictor of death than blood pressure.

In detail

The Prospective Urban Rural Epidemiology (PURE) cohort measured grip with a Jamar dynamometer. Over median 4.0 years, each 11 lb (5 kg) reduction in grip strength was associated with all-cause mortality HR 1.16 (95% CI 1.13-1.20), cardiovascular mortality 1.17, myocardial infarction 1.07 and stroke 1.09. Grip strength was a stronger predictor of all-cause and cardiovascular mortality than systolic blood pressure.

The study · 1

Leong et al., prognostic value of grip strength, findings from the PURE study · Lancet 2015;386(9990):266-73

Measurement And Diagnosis

The 2019 sarcopenia consensus puts low strength ahead of low massModerate · mixed

In plain terms

For years sarcopenia was defined mainly by how much muscle you had. The updated expert consensus puts strength first, because how strong a person is predicts falls, disability and death better than muscle size does.

In detail

The European Working Group on Sarcopenia in Older People (EWGSOP2, 2019) moved low muscle strength to the front of the definition, with low muscle quantity or quality confirming it and poor physical performance marking severity. The change reflected accumulating evidence that strength is more closely tied to adverse outcomes than mass, and it set operational cut-points for grip strength and chair-rise testing.

The study · 1

Cruz-Jentoft et al., sarcopenia, revised European consensus on definition and diagnosis (EWGSOP2) · Age Ageing 2019;48(1):16-31

More relative muscle tracks with steadier blood sugar. In a survey of 13,644 US adults, each 10% higher relative muscle mass came with about 11% lower insulin resistance and about 12% less prediabetes. This is a single snapshot, and cause runs both ways: insulin resistance itself wastes muscle, so the insulin and glucose link runs in both directions. Most type 2 diabetes is not inevitable. In the Nurses' Health Study, about 90% of cases tracked with diet, weight and activity a person can change, much of it built on ultra-processed food. Holding on to muscle is one of the few type 2 diabetes risk factors a person can change directly.

What It Means For You

Build muscle, then keep it. Muscle does its metabolic and endocrine work in proportion to how much of it there is and how well it functions.

Two practices do most of the work, and both are free. Resistance training builds and holds the tissue; enough protein supplies the raw material, and protein matters more with age. Older muscle needs a bigger dose of protein to respond to the same building signal, a state called anabolic resistance. In stable-isotope studies, fully switching on muscle protein synthesis took about 0.40 g of protein per kg per meal in older men, against 0.24 g/kg in young men. Protein synthesis still works in older muscle; it just needs more protein per meal to reach the same response.

Train for strength ahead of size. The 2019 revision of the sarcopenia definition leads with low strength, because strength predicts falls, disability and lost independence better than muscle bulk does. Start with the minimum effective dose of resistance training, turn to protein and muscle for amounts, and know that even walking helps hold what you already have. Do the free, real thing first: losing weight and lifting come before medication. A GLP-1 drug is the fallback for when the real thing is genuinely out of reach.

Go Deeper

The practices and pages that act on this tissue, or use it:

• Resistance training grows the muscle and keeps it from wasting, and its minimum effective dose is the least work that still maintains it.
• Protein and muscle supplies the raw material, and it matters more with age.
• Walking and insulin and glucose use the glucose-clearing role directly, and type 2 diabetes is where it converges.
• Grip strength, a cheap read on whole-body robustness and a marker of it.

Common Questions

Is a strong grip keeping people healthy, or just a sign of it?

Mostly a sign, but a sign you can act on. The Leong 2015 link between grip and survival was observational, so grip signals health without proving it causes it. Yet the strength a grip test reflects responds to resistance work. That whole-body strength is what tracks with staying independent into old age, so training toward a stronger grip is worth the effort.

Does building muscle speed up my metabolism?

Barely. A kilogram of resting muscle burns about 13 calories a day, a few times more than the 4.5 of fat. Adding a few kilograms of muscle raises resting burn only a little; muscle's real metabolic payoff comes from glucose disposal and myokine signaling. Pound for pound, resting muscle burns far less than the liver, at roughly 200 calories a day, or the brain, at about 240.