Open Access

Opening of mitoKATP improves cardiac function and inhibits apoptosis via the AKT-Foxo1 signaling pathway in diabetic cardiomyopathy

  • Authors:
    • Peng Duan
    • Jinxin Wang
    • Yang Li
    • Shiqiang Wei
    • Feng Su
    • Sanlin Zhang
    • Yuhui Duan
    • Lin Wang
    • Qinglei Zhu
  • View Affiliations

  • Published online on: August 21, 2018     https://doi.org/10.3892/ijmm.2018.3832
  • Pages: 2709-2719
  • Copyright: © Duan et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Decreasing phosphorylation of AKT‑Foxo1 is closely associated with the onset of insulin resistance and apoptosis during diabetic cardiomyopathy (DCM). Opening of mitochondrial ATP‑sensitive potassium channels (mitoKATP) increases the expression of p‑AKT in the process of reperfusion injury. It was therefore hypothesized that opening of mitoKATP may regulate the AKT‑Foxo1 signaling pathway and improve cardiac function in DCM. In the present study, opening of mitoKATP by diazoxide (DZX) was found to improve cardiac function and attenuate cardiomyocyte apoptosis in db/db mice. DZX also significantly increased the expression of p‑AKT and p‑Foxo1. Similarly, DZX decreased the expression of the heart failure marker NT‑proBNP, increased mitochondrial membrane potential, inhibited apoptosis, and increased the expression of p‑AKT and p‑Foxo1 when mimicking insulin resistance in cultured cardiomyocytes. Moreover, the protective effects of DZX were completely blocked by the specific AKT inhibitor MK‑2206. These data suggest that the regulation of the AKT‑Foxo1 signaling pathway by mitoKATP plays an important role in improving cardiac function and inhibiting apoptosis in DCM, and may therefore be a new potential therapeutic target for DCM.
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November-2018
Volume 42 Issue 5

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Duan P, Wang J, Li Y, Wei S, Su F, Zhang S, Duan Y, Wang L and Zhu Q: Opening of mitoKATP improves cardiac function and inhibits apoptosis via the AKT-Foxo1 signaling pathway in diabetic cardiomyopathy. Int J Mol Med 42: 2709-2719, 2018.
APA
Duan, P., Wang, J., Li, Y., Wei, S., Su, F., Zhang, S. ... Zhu, Q. (2018). Opening of mitoKATP improves cardiac function and inhibits apoptosis via the AKT-Foxo1 signaling pathway in diabetic cardiomyopathy. International Journal of Molecular Medicine, 42, 2709-2719. https://doi.org/10.3892/ijmm.2018.3832
MLA
Duan, P., Wang, J., Li, Y., Wei, S., Su, F., Zhang, S., Duan, Y., Wang, L., Zhu, Q."Opening of mitoKATP improves cardiac function and inhibits apoptosis via the AKT-Foxo1 signaling pathway in diabetic cardiomyopathy". International Journal of Molecular Medicine 42.5 (2018): 2709-2719.
Chicago
Duan, P., Wang, J., Li, Y., Wei, S., Su, F., Zhang, S., Duan, Y., Wang, L., Zhu, Q."Opening of mitoKATP improves cardiac function and inhibits apoptosis via the AKT-Foxo1 signaling pathway in diabetic cardiomyopathy". International Journal of Molecular Medicine 42, no. 5 (2018): 2709-2719. https://doi.org/10.3892/ijmm.2018.3832