A role for AMP-activated protein kinase in contraction- and hypoxia-regulated glucose transport in skeletal muscle

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.