Glucose uptake into muscle and its subsequent storage as glycogen is a cruc
ial factor in energy homeostasis in skeletal muscle. This process is stimul
ated acutely by insulin and is impaired in both insulin-resistant states an
d in type 2 diabetes mellitus. A signalling pathway involving protein kinas
e B and glycogen synthase kinase 3 seems certain to have a key role in stim
ulating glycogen synthesis but other signalling pathways also contribute, i
ncluding a rapamycin-sensitive pathway stimulated by amino acids. Although
glycogen synthesis is one of the classical insulin-regulated pathways, it i
s also regulated in an insulin-independent manner; for example glycogen syn
thesis in muscle is stimulated significantly after strenuous exercise, with
much of this stimulation being independent of the involvement of insulin.
Evidence suggests that glucose and the glycogen content of the muscle have
a key role in this stimulation but the molecular mechanism has vet to be fu
lly explained.