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October 5, 2004Hypertension

Mechanisms for Increased Glycolysis in the Hypertrophied Rat Heart

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Authors

LNLuigino NascimbenBrigham and Women's HospitalJIJoanne S. IngwallHeart Failure / CardiomyopathyBLBeverly H. LorellHeart Failure / Cardiomyopathy

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Implication

No immediate clinical implications in LVH; leaves open whether targeting energetic stress improves human outcomes.

Key Points

  • To determine the cellular and biochemical mechanisms responsible for increased glycolysis and glucose uptake in pressure-overload left ventricular hypertrophy.
  • Evaluated glycolytic flux and insulin-independent glucose uptake in a rat model of pressure-overload left ventricular hypertrophy.
  • Measured maximal enzyme activity (Vmax) and quantified intracellular concentrations of allosteric activators and inhibitors of phosphofructokinase, including ATP, free ADP, free AMP, inorganic phosphate, and fructose-2,6-bisphosphate.
  • Hypertrophied hearts showed a 2-fold increase in glycolysis rate and a 3-fold increase in insulin-independent glucose uptake without changes in the Vmax of key glycolytic enzymes.
  • Allosteric activators of phosphofructokinase (free ADP, free AMP, inorganic phosphate, and fructose-2,6-bisphosphate) increased up to 10-fold, whereas pathway inhibitors (ATP, citrate, and H+) remained unchanged.
  • Elevated intracellular free ADP and AMP activated the AMP-activated protein kinase pathway, driving fructose-2,6-bisphosphate synthesis and sarcolemmal glucose transporter localization.

Cite This Study

Nascimben et al. (2004) studied this question.

synapsesocial.com/papers/6a7856e1576efb0ddaf807cfhttps://doi.org/10.1161/01.hyp.0000144292.69599.0c
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Also Consider

Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Effects of insulin and work on fructose 2,6-bisphosphate content and phosphofructokinase activity in perfused rat hearts.1987 · 49 citations
  2. 2Increased Adenosine Monophosphate–Activated Protein Kinase Activity in Rat Hearts With Pressure-Overload Hypertrophy2001 · 309 citations
  3. 3Failure to Maintain a Low ADP Concentration Impairs Diastolic Function in Hypertrophied Rat Hearts1997 · 134 citations
  4. 4Translocation of myocardial GLUT-4 and increased glucose uptake through activation of AMPK by AICAR1999 · 553 citations
  5. 5Serial Echocardiographic-Doppler Assessment of Left Ventricular Geometry and Function in Rats With Pressure-Overload Hypertrophy1995 · 310 citations