Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise.
AMP-activated protein kinase (AMPK) is emerging as a key signaling pathway that modulates cellular metabolic processes. In skeletal muscle, AMPK is activated during exercise. Increased myocardial substrate metabolism during exercise could be explained by AMPK activation. Although AMPK is known to be activated during myocardial ischemia, it remains uncertain whether AMPK is activated in response to the physiological increases in cardiac work associated with exercise. Therefore, we evaluated cardiac AMPK activity in rats at rest and after 10 min of treadmill running at moderate (15% grade, 16 m/min) or high (15% grade, 32 m/min) intensity. Total AMPK activity in the heart increased in proportion to exercise intensity (P < 0.05). AMPK activity associated with the alpha2-catalytic subunit increased 2.8 +/- 0.4-fold (P < 0.02 vs. rest) and 4.5 +/- 0.6-fold (P < 0.001 vs. rest) with moderate- and high-intensity exercise, respectively. AMPK activity associated with the alpha1-subunit increased to a lesser extent. Phosphorylation of the Thr172-regulatory site on AMPK alpha-catalytic subunits increased during exercise (P < 0.001). There was no increase in Akt phosphorylation during exercise. The changes in AMPK activity during exercise were associated with physiological AMPK effects (GLUT4 translocation to the sarcolemma and ACC phosphorylation). Thus cardiac AMPK activity increases progressively with exercise intensity, supporting the hypothesis that AMPK has a physiological role in the heart.
Coven
David L
DL
Section of Cardiovascular Medicine, Department of Internal Medicine, Yale University School of Medicine, New Haven, CT 06510, USA.
Hu
Xiaoyue
X
Cong
Lin
L
Bergeron
Raynald
R
Shulman
Gerald I
GI
Hardie
D Grahame
DG
Young
Lawrence H
LH
D055372:AMP-Activated Protein Kinases; D000818:Animals; D004734:Energy Metabolism / Q000502:physiology; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4; D006003:Glycogen / Q000378:metabolism; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000378:metabolism; D009097:Multienzyme Complexes / Q000378:metabolism*; D009124:Muscle Proteins; D009206:Myocardium / Q000201:enzymology*; D010766:Phosphorylation; D005082:Physical Exertion / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000502:physiology
D051275:Glucose Transporter Type 4; D009004:Monosaccharide Transport Proteins; D009097:Multienzyme Complexes; D009124:Muscle Proteins; C495694:Slc2a4 protein, rat; D006003:Glycogen; D017346:Protein Serine-Threonine Kinases; D055372:AMP-Activated Protein Kinases; D005947:Glucose