LAUSR

Muscle tissue utilizes glucose as a fuel during exercise and stores glucose in form of glycogen during rest. The associated glucose transport includes delivery of glucose from blood plasma into the interstitial space and subsequent, GLUT‐4 facilitated diffusion into muscle cells. The extent to which the vascular endothelium acts as a barrier to glucose transport, however, remains debated. While accurate measurements of interstitial glucose concentration (IGC) are key to resolve this debate, these are also challenging as removal of interstitial fluid may perturb glucose transport and therefore bias IGC measurements. We developed a three‐compartment model to infer IGC in skeletal muscle from its local metabolism and blood flow. The model predicts that IGC remains within 5% of that of blood plasma during resting conditions but decreases more as metabolism increases. Next, we determined how microdialysis protocols affect IGC. Our model analysis suggests that microdialysis‐based IGC measurements underestimate true values. Notably, reported increases in muscle capillary permeability surface area product (PS) to glucose under the condition of elevated metabolism may owe in part to such measurements bias.