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Article

AMPK activation restores ischemic post‑conditioning cardioprotection in STZ‑induced type 1 diabetic rats: Role of autophagy

  • Authors:
    • Bin Zhou
    • Yan Leng
    • Shao‑Qing Lei
    • Zhong‑Yuan Xia
  • View Affiliations / Copyright

    Affiliations: Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
  • Pages: 3648-3656
    |
    Published online on: July 18, 2017
       https://doi.org/10.3892/mmr.2017.7033
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Abstract

Although the mechanism remains unclear, ischemic post‑conditioning (IPO) is a promising approach to combat myocardial ischemia reperfusion (IR) injury; however, it has been proven ineffective in diabetes. The present study aimed to identify whether hyperglycemia‑induced AMP‑activated protein kinase (AMPK) inhibition contributes to the ineffectiveness of IPO via autophagy attenuation in diabetic hearts. Diabetic and non‑diabetic rats were subjected to myocardial IR and/or IPO with/without treatment with the AMPK activator A‑769662 and/or autophagy inhibitor 3‑methyladenine (3‑MA). Rat cardiomyocyte H9c2 cells were pretreated with A‑769662 and/or 3‑MA, and subjected to hypoxia reoxygenation (HR) or hypoxia post‑conditioning (HPO). The degree of injury to the myocardium/cells, oxidative stress, AMPK/mammalian target of rapamycin (mTOR) signaling and autophagy status were analyzed. In diabetic rats the myocardial infarct size, and creatine kinase‑MB and malondialdehyde release, were increased compared with non‑diabetic rats, concomitant with increased cardiac dysfunction and decreased cardiac superoxide dismutase activity, AMPK phosphorylation and autophagy following IR. IPO attenuated myocardial infarct size, increased AMPK phosphorylation and enhanced autophagy in non‑diabetic animals. A‑769662 (6.0 mg/kg) restored IPO cardioprotection in diabetic rats. In vitro, HPO combined with A‑769662 decreased HR injury in H9c2 cells exposed to high glucose, as evidenced by decreased lactic dehydrogenase expression and oxidative stress, accompanied by increased cell viability and autophagy. The A‑769662‑mediated restoration of IPO/HPO cardioprotection was completely reversed by treatment with the autophagy inhibitor 3‑MA. In conclusion, AMPK inhibition, by decreasing autophagy, may be a mechanism through which diabetic hearts are rendered unresponsive to IPO cardioprotection.
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Copy and paste a formatted citation
Spandidos Publications style
Zhou B, Leng Y, Lei SQ and Xia ZY: AMPK activation restores ischemic post‑conditioning cardioprotection in STZ‑induced type 1 diabetic rats: Role of autophagy. Mol Med Rep 16: 3648-3656, 2017.
APA
Zhou, B., Leng, Y., Lei, S., & Xia, Z. (2017). AMPK activation restores ischemic post‑conditioning cardioprotection in STZ‑induced type 1 diabetic rats: Role of autophagy. Molecular Medicine Reports, 16, 3648-3656. https://doi.org/10.3892/mmr.2017.7033
MLA
Zhou, B., Leng, Y., Lei, S., Xia, Z."AMPK activation restores ischemic post‑conditioning cardioprotection in STZ‑induced type 1 diabetic rats: Role of autophagy". Molecular Medicine Reports 16.3 (2017): 3648-3656.
Chicago
Zhou, B., Leng, Y., Lei, S., Xia, Z."AMPK activation restores ischemic post‑conditioning cardioprotection in STZ‑induced type 1 diabetic rats: Role of autophagy". Molecular Medicine Reports 16, no. 3 (2017): 3648-3656. https://doi.org/10.3892/mmr.2017.7033
Copy and paste a formatted citation
x
Spandidos Publications style
Zhou B, Leng Y, Lei SQ and Xia ZY: AMPK activation restores ischemic post‑conditioning cardioprotection in STZ‑induced type 1 diabetic rats: Role of autophagy. Mol Med Rep 16: 3648-3656, 2017.
APA
Zhou, B., Leng, Y., Lei, S., & Xia, Z. (2017). AMPK activation restores ischemic post‑conditioning cardioprotection in STZ‑induced type 1 diabetic rats: Role of autophagy. Molecular Medicine Reports, 16, 3648-3656. https://doi.org/10.3892/mmr.2017.7033
MLA
Zhou, B., Leng, Y., Lei, S., Xia, Z."AMPK activation restores ischemic post‑conditioning cardioprotection in STZ‑induced type 1 diabetic rats: Role of autophagy". Molecular Medicine Reports 16.3 (2017): 3648-3656.
Chicago
Zhou, B., Leng, Y., Lei, S., Xia, Z."AMPK activation restores ischemic post‑conditioning cardioprotection in STZ‑induced type 1 diabetic rats: Role of autophagy". Molecular Medicine Reports 16, no. 3 (2017): 3648-3656. https://doi.org/10.3892/mmr.2017.7033
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