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Acute hyperglycemia abolishes ischemic preconditioning by inhibiting Akt phosphorylation: normalizing blood glucose

Zequan Yang1, Yikui Tian2, Yuan Liu2

  • 1Department of Surgery, University of Virginia Health System, P.O. Box 800709, Charlottesville, VA 22908, USA ; Department of Biomedical Engineering, University of Virginia Health System, P.O. Box 800759, Charlottesville, VA 22908, USA.

Oxidative Medicine and Cellular Longevity
|December 28, 2013
PubMed

Insights

Acute hyperglycemia (high blood sugar) blocks the heart-protective effects of ischemic preconditioning (IPC) by inhibiting Akt phosphorylation. Restoring normal blood glucose levels with insulin recovers this protective benefit.

Area of Science:

  • Cardiovascular Research
  • Metabolic Studies
  • Molecular Cardiology

Background:

  • Ischemic preconditioning (IPC) is a phenomenon that protects the heart from ischemic injury.
  • The precise mechanisms by which hyperglycemia (HG) interferes with IPC are not fully understood.
  • Akt phosphorylation is a key signaling pathway involved in cardioprotection.

Purpose of the Study:

  • To investigate whether acute hyperglycemia inhibits the cardioprotective effects of IPC.
  • To determine if Akt phosphorylation is the mechanism underlying this inhibition.
  • To assess if normalizing blood glucose can restore the protective effects of IPC.

Main Methods:

  • Acute hyperglycemia was induced in C57BL/6 mice using dextrose injection.
  • Mice underwent a standard IPC protocol followed by myocardial infarction (ischemia-reperfusion).
  • Infarct size and cardiac Akt phosphorylation levels were measured. Some groups received insulin or CCPA.

Main Results:

  • IPC significantly reduced infarct size in control mice.
  • Hyperglycemia exacerbated infarct size and abolished the protective effect of IPC.
  • IPC-induced Akt phosphorylation was inhibited by hyperglycemia, an effect reversed by insulin.
  • CCPA mimicked IPC's cardioprotective effect, which was also abolished by hyperglycemia.

Conclusions:

  • Acute hyperglycemia abolishes the cardioprotective effect of ischemic preconditioning.
  • This inhibition is mediated by the suppression of Akt phosphorylation.
  • Restoring normal blood glucose levels with insulin is sufficient to recover the cardioprotective effects of IPC.
Abstract

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