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Oxidative Medicine and Cellular Longevity
Volume 2013, Article ID 329183, 8 pages
http://dx.doi.org/10.1155/2013/329183
Research Article

Acute Hyperglycemia Abolishes Ischemic Preconditioning by Inhibiting Akt Phosphorylation: Normalizing Blood Glucose before Ischemia Restores Ischemic Preconditioning

1Department of Surgery, University of Virginia Health System, P.O. Box 800709, Charlottesville, VA 22908, USA
2Department of Biomedical Engineering, University of Virginia Health System, P.O. Box 800759, Charlottesville, VA 22908, USA

Received 17 August 2013; Accepted 5 November 2013

Academic Editor: Qian Fan

Copyright © 2013 Zequan Yang et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

This study examined the hypothesis that acute hyperglycemia (HG) blocks ischemic preconditioning (IPC) by inhibiting Akt phosphorylation. Brief HG of approximately 400 mg/dL was induced in C57BL/6 mice via intraperitoneal injection of 20% dextrose (2 g/kg). All mice underwent 40 min LAD occlusion and 60 min reperfusion. The IPC protocol was 2 cycles of 5 min ischemia and 5 min reperfusion prior to index ischemia. Results. In control mice, infarct size (IF) was 51.7 ± 2.0 (% risk region). Preconditioning reduced IF by 50% to 25.8 ± 3.2 ( versus control). In HG mice, IF was significantly exacerbated to 58.1 ± 2.3. However, the effect of IPC completely disappeared in HG mice. Normalization of blood glucose with insulin 5 min before IPC recovered the cardioprotective effect. Administration of CCPA before index ischemia mimicked IPC effect. The cardioprotective effect of CCPA, not its chronotropic effect, completely disappeared in HG mice. Phosphorylation of cardiac tissue Akt before index ischemia was enhanced by IPC or CCPA but was significantly inhibited by HG in both groups. Normalization of glucose with insulin reversed the inhibition of Akt phosphorylation by HG. Conclusion. HG abolishes the cardioprotective effect of preconditioning by inhibiting Akt phosphorylation. Normalization of blood glucose with insulin suffices to recover the cardioprotective effect of preconditioning.