In human muscle cells, leucine by itself does not change the activity of AKT, GSK3β, or glycogen synthesis, but when insulin is present, it temporarily increases ERK1/2 phosphorylation, with the...

Pro

Against

Mechanism

Synthesis from 1 study

How it works

Leucine doesn’t turn on insulin’s main energy-storage signals, but it makes a short-lived side signal—ERK—stronger for about 10 minutes when insulin is around. After that, everything goes back to normal, and no other insulin effects are changed.

Most probable mechanism

In Simple Terms

When insulin is present, leucine makes the ERK signal stronger and faster, but only for a short time—peaking at 10 minutes and then stopping—without changing other insulin-related signals like AKT or glycogen production.

Causal chain

Insulin binds to its receptor on the muscle cell membrane, activating the Grb2-SOS-Ras-Raf-MEK signaling cascade that leads to ERK1/2 phosphorylation.

Verified by multiple studies

which leads to

Leucine pre-exposure amplifies the activation of this cascade, increasing the peak level of ERK1/2 phosphorylation without altering the baseline activity of the pathway.

Verified by multiple studies

which leads to

The amplified ERK1/2 phosphorylation is rapidly terminated through feedback mechanisms, such as phosphatase activity or inhibitor recruitment, causing levels to return to baseline within 60 minutes.

Verified by multiple studies

which leads to

Leucine does not activate or enhance the PI3K-AKT-GSK3β pathway, nor does it increase glycogen synthesis in the absence of insulin, and even with insulin, it does not prolong AKT or GSK3β phosphorylation beyond the insulin-only response.

Verified by multiple studies

Evidence from Studies

Supporting (1)

Community contributions welcome

Leucine modulates dynamic phosphorylation events in insulin signaling pathway and enhances insulin-dependent glycogen synthesis in human skeletal muscle cells

Cross-Sectional Study

In Vitro

2014 Mar 20

Contradicting (0)

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No contradicting evidence found

Gold Standard Evidence Needed

According to GRADE and EBM methodology, here is what ideal scientific evidence would look like to definitively prove or disprove this specific claim, ordered from strongest to weakest evidence.

Source Study

Leucine modulates dynamic phosphorylation events in insulin signaling pathway and enhances insulin-dependent glycogen synthesis in human skeletal muscle cells

Score: 7

DOI: 10.1186/1471-2121-15-9

Similar Assertions

At a concentration of 100 micromolar, leucine produces the maximum possible increase in insulin-driven GSK3β phosphorylation and glycogen synthesis in human muscle cells; higher concentrations up to 400 micromolar do not produce a greater effect.

89%

In human muscle cells deprived of nutrients, adding 100 micromolar leucine before insulin increases the activation of key signaling proteins and boosts glycogen production by 50% compared to insulin alone.

88%

When human muscle cells are exposed to leucine before insulin stimulation, there is an increase in the phosphorylation of a specific protein site (4EBP1 at Thr37/46), but this increase is not consistently observed across all experiments and cannot be detected when only a single time point is measured.

77%

Leucine, an amino acid, triggers a cellular pathway called mTOR that starts the production of muscle proteins. When carbohydrates are consumed at the same time, the resulting increase in insulin levels boosts this process.

75%

Insulin helps move certain proteins to the surface of human muscle cells and boosts their activity, and this seems to involve a specific cellular signaling process.

72%