Eukaryotic cells possess systems for sensing nutritional stress and inducin
g compensatory mechanisms that minimize the consumption of ATP while utiliz
ing alternative energy sources. Such stress can also be imposed by increase
d energy needs, such as in skeletal muscle of exercising animals. In these
studies, we consider the role of the metabolic sensor, AMP-activated protei
n kinase (AMPK), in the regulation of glucose transport in skeletal muscle.
Expression in mouse muscle of a dominant inhibitory mutant of AMPK complet
ely blocked the ability of hypoxia or AICAR to activate hexose uptake, whil
e only partially reducing contraction-stimulated hexose uptake. These data
indicate that AMPK transmits a portion of the signal by which muscle contra
ction increases glucose uptake, but other AMPK-independent pathways also co
ntribute to the response.