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...

Pro

Against

Mechanism

Synthesis from 1 study

How it works

When muscle cells are starved, a specific amount of leucine makes them more responsive to insulin. This lets insulin turn on a chain of signals that ultimately removes a brake on glycogen production, allowing the cells to store much more energy as glycogen.

Most probable mechanism

In Simple Terms

When muscle cells are low on nutrients, a specific amount of leucine prepares the cell to respond more strongly to insulin. This makes insulin more effective at turning on a key protein called AKT, which then turns off another protein called GSK3β. When GSK3β is turned off, it stops blocking the enzyme that builds glycogen, allowing the cell to store much more energy as glycogen.

Causal chain

Leucine pre-exposure enhances the sensitivity of the insulin signaling cascade, increasing the magnitude of insulin receptor activation or proximal signal amplification without directly activating it alone.

Verified by multiple studies

which leads to

Insulin binding triggers phosphoinositide 3-kinase (PI3K)-dependent phosphorylation of AKT at Ser473, a step whose magnitude and duration are amplified by prior leucine exposure.

Verified by multiple studies

which leads to

Phosphorylated AKT directly phosphorylates GSK3β at Ser21/9, leading to its inactivation.

Verified by multiple studies

which leads to

Inactivated GSK3β no longer inhibits glycogen synthase, allowing glycogen synthase to remain active and catalyze the polymerization of glucose into glycogen.

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

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 highest effect at 10 minutes and no effect remaining after 60 minutes.

88%

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.

86%

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.

77%

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%

When insulin is infused into healthy young adults without providing amino acids, the levels of key amino acids in the blood drop by 40–50% within 7 hours, and this is accompanied by a decrease in muscle protein synthesis and no activation of the mTOR signaling pathway.

71%