The stimulation of heart glycolysis by increased workload does not require AMP-activated protein kinase but a wortmannin-sensitive mechanism.
Increasing heart workload stimulates glycolysis by enhancing glucose transport and fructose-2,6-bisphosphate (Fru-2,6-P(2)), the latter resulting from 6-phosphofructo-2-kinase (PFK-2) activation. Here, we investigated whether adenosine monophosphate (AMP)-activated protein kinase (AMPK) mediates PFK-2 activation in hearts submitted to increased workload. When heart work was increased, PFK-2 activity, Fru-2,6-P(2) content and glycolysis increased, whereas the AMP:adenosine triphosphate (ATP) and phosphocreatine/creatine (PCr:Cr) ratios, and AMPK activity remained unchanged. Wortmannin, the well-known phosphatidylinositol-3-kinase inhibitor, blocked the activation of protein kinase B and the increase in glycolysis and Fru-2,6-P(2) content induced by increased work. Therefore, the control of heart glycolysis by contraction differs from that in skeletal muscle where AMPK is involved.
Beauloye
Christophe
C
Hormone and Metabolic Research Unit, Christian de Duve Institute of Cellular Pathology, ICP-UCL 7529, 75, avenue Hippocrate, Brussels, Belgium.
Marsin
Anne Sophie
AS
Bertrand
Luc
L
Vanoverschelde
Jean Louis
JL
Rider
Mark H
MH
Hue
Louis
L
D055372:AMP-Activated Protein Kinases; D000730:Androstadienes / Q000494:pharmacology*; D000818:Animals; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006019:Glycolysis; D006321:Heart / Q000187:drug effects / Q000502:physiology*; D006439:Hemodynamics; D007700:Kinetics; D008297:Male; D009097:Multienzyme Complexes / Q000502:physiology*; D009206:Myocardium / Q000201:enzymology* / Q000378:metabolism; D025481:Phosphofructokinase-2 / Q000378:metabolism; D000081082:Phosphoinositide-3 Kinase Inhibitors; D017346:Protein Serine-Threonine Kinases / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt; D051381:Rats; D017208:Rats, Wistar; D000077191:Wortmannin
D000730:Androstadienes; D004791:Enzyme Inhibitors; D009097:Multienzyme Complexes; D000081082:Phosphoinositide-3 Kinase Inhibitors; D011518:Proto-Oncogene Proteins; D025481:Phosphofructokinase-2; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D000077191:Wortmannin