5'-AMP Activated Protein Kinase is a Key Mediator of Post-Exercise Insulin Sensitivity in Mouse Skeletal Muscle
Abstract Number: 1034-P
Authors: TARO TOYODA, DING AN, JOSEF BRANDAUER, HO-JIN KOH, NOBUHARU FUJII, MICHAEL F. HIRSHMAN, LAURIE J. GOODYEAR, Boston, MA
Institutions: Boston, MA
Results: The effects of exercise to increase glucose uptake into skeletal muscle occurs in two phases, the first phase is insulin-independent, and reverses rapidly. The second phase is evident after the insulin-independent phase has ended, and is characterized by increased submaximal insulin-stimulated glucose uptake. The mechanism for this enhanced post-exercise insulin sensitivity is not fully understood. We used skeletal muscle-specific transgenic mice with ablated 5'-AMP activated protein kinase (AMPK) α2 activity (TG) to determine whether AMPK is necessary for enhanced post-exercise insulin sensitivity. Since TG mice have impaired exercise capacity, our initial experiment was to establish an exercise protocol that was tolerable to these animals. We found that TG mice could perform 30 min of low intensity treadmill exercise (0.3 mph, 0% slope), and subsequent studies used this protocol. Using wild type mice, we next determined the time point when the insulin-independent effects of exercise on glucose uptake have subsided and insulin sensitivity is increased. Wild type mice were exercised or remained sedentary, soleus muscles were isolated and incubated in oxygenated Krebs buffer and 2-deoxyglucose uptake was measured. By 70 min post-exercise, glucose uptake in the absence of insulin was not different between sedentary and post-exercise muscles, showing that the acute effect of exercise had reversed. At 70 min post-exercise there was increased insulin sensitivity, as submaximal (250 μU/ml) insulin-stimulated glucose uptake was significantly increased in the post-exercise group compared to the sedentary. The low intensity exercise protocol significantly increased AMPKα2 activity (112%) and acetyl-CoA carboxylase phosphorylation (71%), which were also reversed by 70 min post-exercise. This protocol was next used to compare post-exercise insulin sensitivity in TG mice and wild type littermates (WT). Submaximal insulin-stimulated glucose uptake post-exercise was increased by 60% in WT (p < 0.05), but not in TG mice (13%, NS). Glycogen content after exercise was similar between the WT and TG mice. These results suggest that AMPKα2 is a key component regulating post-exercise insulin sensitivity for glucose uptake in mouse skeletal muscle.