In older adults with insulin resistance, consuming protein and doing resistance exercise causes a larger spike in insulin than in younger adults, but this higher insulin level does not lead to better...
Mechanism
Synthesis from 1 study
When older adults eat protein and lift weights, their insulin spikes higher than in younger people, but their muscles don’t build more protein because a key signal blocker called IP6K1 stays too high. This blocks the chain of events that lets amino acids turn into muscle, even though there’s plenty...
Most probable mechanism
In older adults with insulin resistance, eating protein and doing strength training causes a big spike in insulin, but their muscles don’t use the protein well because a key signaling molecule called IP6K1 doesn’t respond properly. Normally, after eating, IP6K1 drops so that amino acids can enter muscle cells and trigger muscle building. In older adults, IP6K1 stays high or doesn’t drop enough, which blocks a critical protein called Akt from turning on. Without Akt, the cell can’t activate the machinery that builds new muscle proteins, even though there’s plenty of insulin and amino acids around.
Protein ingestion and resistance exercise trigger a rise in plasma insulin in older adults, but this response is exaggerated compared to young adults.
In older adults, muscle and plasma levels of IP6K1 remain elevated or fail to decrease after protein intake and exercise, unlike in young adults where IP6K1 declines.
Elevated IP6K1 increases production of IP7, which binds to the PH domain of Akt and prevents its recruitment to the cell membrane.
Blocked Akt translocation reduces its phosphorylation at Thr308, impairing downstream activation of mTORC1.
Reduced mTORC1 activity decreases phosphorylation of 4E-BP1, limiting the release of eIF4E and suppressing the initiation of mRNA translation for muscle protein synthesis.
The failure to upregulate LAT1, the amino acid transporter that brings leucine into muscle cells, further limits mTORC1 activation and amino acid disposal.
Despite high insulin levels, phenylalanine rate of disappearance is reduced, indicating impaired amino acid uptake and utilization by muscle tissue.
Evidence from Studies
Supporting (1)
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Inositol hexakisphosphate kinase 1 is implicated in the insulin response to protein ingestion in older adults
Contradicting (0)
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