Modulation of Skeletal Muscle Fatigue Kinetics by Extracellular Glucose and Glycogen Content

Increasing activity and the demand on skeletal muscle invariably leads to a depletion of energy reserves and a reduction in the ability of the muscle to produce force, known as muscle fatigue. Studies have shown glycogen to be of integral importance to this process and to play a role that is more complex than as a simple glucose reservoir. Here, using mouse FDB muscle bundles, we investigated the respective influence of glycogen and extracellular glucose on muscle fatigue. During a first bout of fatigue (FAT1) glycogen usage and force production was similar between control and insulin‐exposed muscles. Glycogen replenishment 60 min after FAT1 was such that glycogen content prior to a second fatigue bout (FAT2) and the amount used during FAT2 was greater than for FAT1. This corresponded to an increase in time to fatigue. For a low glycogen model, FAT1 was followed by a 60 min recovery period in 0 glucose, resulting in a decline in pre‐FAT2 glycogen content. When FAT2 was elicited also in 0 glucose, a marked decrease in time to fatigue was observed, which was partially recovered when if glucose was reintroduced 10 min before FAT2, to spite very low glycogen content and usage. A correlation was revealed when pre‐FAT glycogen content and time to fatigue were compared for FAT2 bouts. From these results, we support that glycogen is a consistently critical factor in muscle fatigue, and suggest that extracellular glucose cannot fully compensate for force loss after excessive glycogen depletion.