When muscle that has recently been exercised is exposed to high levels of glucose and insulin in a controlled lab environment, its ability to take up glucose in response to insulin is reduced,...
Mechanism
Synthesis from 1 study
After exercise, muscle is primed to take up sugar efficiently, but if sugar and insulin stay high, they trigger a biochemical process that adds a molecular tag to key proteins. This tag blocks insulin’s signal, preventing sugar from entering the muscle cells and canceling the exercise benefit.
Most probable mechanism
After exercise, muscle becomes more sensitive to insulin, but if sugar and insulin levels stay high right after, a biochemical pathway gets overactivated. This pathway adds a chemical tag to key proteins involved in moving sugar into the muscle, which blocks insulin’s signal and stops sugar from entering the cells.
Elevated glucose and insulin levels in the muscle tissue increase the flow of glucose into the hexosamine biosynthetic pathway.
The rate-limiting enzyme of this pathway produces increased levels of UDP-GlcNAc, a sugar donor molecule.
UDP-GlcNAc is used to attach O-GlcNAc modifications to serine and threonine residues on insulin signaling proteins, including IRS1 and Munc18c.
O-GlcNAcylation of IRS1 interferes with its ability to be activated by insulin through tyrosine phosphorylation.
O-GlcNAcylation of Munc18c disrupts the fusion of GLUT4-containing vesicles with the cell membrane.
Reduced GLUT4 translocation to the cell surface decreases the rate of insulin-stimulated glucose uptake.
Evidence from Studies
Supporting (1)
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Seeking the Mechanism for Reversal of Enhanced Insulin Sensitivity after Acute Exercise
Contradicting (0)
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