Insulin resistance accompanies atrophy in slow twitch skeletal muscles such as the soleus. Using a rat hindlimb suspension model of atrophy, we have previously shown that an upregulation of JNK occurs in atrophic muscles and correlates with the degradation of insulin receptor substrate-1 (IRS-1), suggesting that insulin-dependent glucose uptake may be impaired. However, during atrophy, these muscles preferentially use carbohydrates as a fuel source. To investigate this apparent dichotomy, we examined insulin-independent pathways involved in glucose uptake following a two- to 13-week hindlimb suspension regimen. JNK activity was elevated throughout the time course, and IRS-1 was degraded as early as two weeks. AMPK activity was significantly higher in atrophic soleus muscle, as were the activities of the Erk1/2 and p38 MAP kinases. As a comparison, we examined the kinase activity in solei of rats exposed to hypergravity conditions (2G). IRS-1 phosphorylation, protein and AMPK activity was not affected by 2G, demonstrating that these changes were only observed in soleus muscle from hindlimb suspended animals. To further examine the affect of AMPK activation on glucose uptake, C2C12 myotubes were treated with the AMPK activator metformin then challenged with the JNK activator anisomycin. While anisomycin reduced insulinstimulated glucose uptake to control levels, metformin significantly increased glucose uptake in the presence of anisomycin and was independent of insulin. Taken together, these results suggest that AMPK may be an important mediator of insulin-independent glucose uptake in soleus during skeletal muscle atrophy.