Endurance energy supply

Glucose transport

Muscles use glucose taken from the bloodstream as a major energy source during enduring physical exercise.

Glucose transporters in skeletal muscles are therefor rate-limiting factors in endurance performance.

 

Carriers of the SLC2A4/GLUT4 gene variant show higher basal levels of glucose transporters, as well as faster increase in number of transporters in response to training.

The SLC2A4 (aka GLUT4) is a principal glucose transporter protein and a known rate-limiting factor for endurance performance.

SLC2A4 protein levels increase rapidly in response to exercise, and in general it is much more abundant in athletes than in untrained individuals.

Gene: SOLUTE CARRIER FAMILY 2 (FACILITATED GLUCOSE TRANSPORTER), MEMBER 4; (SLC2A4)

Genomic coordinates (GRCh38): 17:7,281,734-7,288,047

Studies found that aerobic exercise promote SLC2A4/GLUT4 gene expression. As shown in the figure below,  SLC4A2/GLUT4 is mainly recruited by MHC I muscle fibers, a muscle type associated with endurance training:

Carriers of the SLC2A4 variant were found to have higher basal levels of glucose transporters, as well as higher-than-average increase in number of transporters in response to training.

The tested SLC2A4 variant is situated in the gene’s promotor, effecting the rate of the gene's transcription, and consequently the number of SLC2A4 transporters available.  As can be seen below, promoter with the A allele produced significantly greater relative activity than that with G allele.

On top of the biochemical evidence, epidemiological studies show that the SLC2A4 allele is more common among endurance athletes, in comparison with controls. This provides another evidence for the role of this gene variant in endurance performance.