EXERCISE INCREASES NUCLEAR AMPK ABUNDANCE IN HUMAN SKELETAL MUSCLE

Sean L. McGee¹, Kirsten F. Howlett¹, Rebecca L. Starkie¹, David Cameron-Smith¹, Bruce E. Kemp², Mark Hargreaves¹, 1 Exercise, Muscle and Metabolism Unit, School of Health Sciences, Deakin University, Burwood, Victoria, 2 St. Vincent's Institute of Medical Research, St. Vincent's Hospital, Fitzroy, Victoria.

Skeletal muscle glucose transport is primarily mediated by the transmembrane glucose transporter GLUT-4. Overexpression of GLUT-4 in skeletal muscle improves whole body insulin action and glucose homeostasis^{1, 2}. Consequently, increasing skeletal muscle GLUT-4 is seen as a potential mechanism to treat and manage type 2 diabetes. Exercise is known to increase both GLUT-4 gene³ and protein⁴ expression. Recent studies have shown an association between increased GLUT-4 expression and the AMP-activated protein kinase (AMPK)^{5, 6}, the activity of which is increased in response to exercise⁷. AMPK activation has also been associated with enhanced expression of other metabolic genes, such as mitochondrial enzymes⁸. It has been hypothesised that AMPK might regulate gene expression through direct interaction with the nucleus. The purpose of this study was to determine if nuclear AMPK α₂ content was increased in human skeletal muscle, in response to an exercise bout that we have previously found to increase GLUT-4 gene expression³. Six male subjects (20.6±2.1 yrs; 72.9±2.1 kg; 180±3 cm, VO_2peak = 3.62±0.18 l.min^-1) cycled for 60 min at 72±1% of VO_2peak. Immediately after exercise, nuclear AMPK α₂ content was increased 1.9±0.4 fold (p = 0.024). There was no change in whole cell AMPK α₂ content or AMPK α₂ mRNA abundance. These results suggest that the nuclear translocation of AMPK might mediate the effects of exercise on skeletal muscle gene and protein expression.

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