In rats, after exercise and eating carbohydrates, the hexosamine biosynthetic pathway is the most likely biological mechanism responsible for restoring normal insulin sensitivity, based on increased...
Mechanism
Synthesis from 1 study
After exercise and eating carbs, too much sugar gets turned into a tag that sticks to insulin's signaling proteins, blocking them from telling muscle cells to absorb glucose. This undoes the improved insulin sensitivity from exercise, and no other sugar-processing pathway shows the same effect.
Most probable mechanism
After exercise and eating a lot of carbs, excess sugar in the blood gets redirected into a special pathway that adds a sugar tag to key proteins involved in insulin signaling. This tag blocks insulin from telling muscle cells to take up glucose, undoing the improved sensitivity caused by exercise.
High glucose and insulin levels following carbohydrate intake after exercise increase the flux of fructose-6-phosphate into the hexosamine biosynthetic pathway.
The rate-limiting enzyme in this pathway converts fructose-6-phosphate and glutamine into UDP-GlcNAc, elevating its intracellular concentration.
UDP-GlcNAc serves as a substrate for the addition of O-GlcNAc modifications to serine and threonine residues on insulin signaling proteins, including IRS1 and Munc18c.
O-GlcNAcylation of IRS1 interferes with its tyrosine phosphorylation, disrupting downstream insulin signal transduction.
O-GlcNAcylation of Munc18c impairs the fusion of GLUT4-containing vesicles with the plasma membrane.
Reduced GLUT4 translocation to the cell surface decreases insulin-stimulated glucose uptake in skeletal muscle.
Evidence from Studies
Supporting (1)
Community contributions welcome
Seeking the Mechanism for Reversal of Enhanced Insulin Sensitivity after Acute Exercise
Contradicting (0)
Community contributions welcome
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.