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...
Mechanism
Synthesis from 3 studies
Leucine turns on the main switch for building muscle protein, but insulin makes that switch work harder and last longer. Without leucine, insulin can't turn on the switch at all — they need each other to make muscle grow.
Most probable mechanism
When leucine enters muscle cells, it triggers a molecular switch that moves a key protein complex to the cell's edge, where it becomes active and starts building new muscle proteins. If insulin is also present, it strengthens this signal by making the switch more sensitive and keeping it active longer, which helps the cell make even more protein and store energy as glycogen.
Leucine is taken up by skeletal muscle cells and binds to intracellular sensors that release inhibition of the GATOR2 complex, enabling activation of the Rag GTPases.
Activated Rag GTPases recruit the mTORC1 complex to the lysosomal surface and cell periphery, where it encounters upstream activators and becomes fully active.
Insulin binds to its receptor on the muscle cell membrane, activating the PI3K-Akt pathway, which enhances mTORC1 activation by relieving inhibitory signals and promoting substrate accessibility.
Activated mTORC1 phosphorylates downstream targets including RPS6 and 4EBP1, initiating ribosomal assembly and mRNA translation to drive myofibrillar protein synthesis.
Insulin further amplifies anabolic signaling by enhancing phosphorylation of AKT and inactivating GSK3β, which supports glycogen synthesis and sustains the cellular environment for protein production.
Evidence from Studies
Supporting (3)
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Insulin fails to enhance mTOR phosphorylation, mitochondrial protein synthesis, and ATP production in human skeletal muscle without amino acid replacement.
Leucine ingestion promotes mTOR translocation to the periphery and enhances total and peripheral RPS6 phosphorylation in human skeletal muscle
Leucine modulates dynamic phosphorylation events in insulin signaling pathway and enhances insulin-dependent glycogen synthesis in human skeletal muscle cells
Contradicting (0)
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