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Role of the PKCβII/JNK signaling pathway in acute glucose fluctuation-induced apoptosis of rat vascular endothelial cells

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Abstract

Aims

The purpose of this study was to investigate the mechanism of vascular endothelial cell apoptosis induced by acute blood glucose fluctuation.

Methods

Thirty rats were assigned to three groups: normal saline (SAL group), constant high glucose (CHG group) and acute blood glucose fluctuation (AFG) group. Other forty rats were assigned to SAL group, AFG group, LY group (PKCβ inhibitor LY333531 was injected intragastrically to the rats who were under acute blood glucose fluctuation) and SP group (JNK inhibitor SP600125 was injected intraperitoneally to the rats who were under acute blood glucose fluctuation). Oxidative stress and inflammatory cytokines were detected. TUNEL was performed to detect apoptosis. Pro-caspase-3, caspase-3 p17, JNK, PKC-βII and insulin signaling-related protein expression were tested by Western blotting.

Results

After administration of LY333531, AFG-induced membrane translocation of PKCβII protein was inhibited, but SP600125 failed to affect AFG-induced PKCβII membrane translocation. After administration of LY333531, the AFG-induced increase in JNK activity was significantly compromised. LY333531 inhibited AFG-induced oxidative stress. However, SP600125 only slightly inhibited AFG-induced oxidative stress reaction (P > 0.05). Both LY333531 and SP600125 can reverse AFG-induced endothelial cell apoptosis increase, inflammatory cytokines levels rise and insulin signaling impairment.

Conclusions

It is necessary to actively control blood glucose and avoid significant glucose fluctuation. PKCβII/JNK may serve as a target, and inhibitors of PKCβII/JNK may be used to help prevent cardiovascular diseases in patients with poor glucose control or significant glucose fluctuation.

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Acknowledgements

The research was supported by Grants from Project of Liaoning Provincial Educational Bureau (LK201603, LK201633, L2015568).

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Authors and Affiliations

  1. Department of Endocrinology, Shengjing Hospital of China Medical University, Shenyang, 110004, China

    Na Wu, Yanjun Wang, Bing He, Yongyan Zhang, Yu Bai, Runyu Du, Qiang Du & Ping Han

  2. Department of Emergency, Shengjing Hospital of China Medical University, Shenyang, 110004, China

    Haitao Shen

Authors
  1. Na Wu
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  2. Haitao Shen
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  3. Yanjun Wang
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  4. Bing He
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  5. Yongyan Zhang
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  6. Yu Bai
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  7. Runyu Du
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  8. Qiang Du
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  9. Ping Han
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Corresponding author

Correspondence to Ping Han.

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The authors declare that they have no conflict of interest.

Ethical standard

This article does not contain any study with human participants. All procedures performed in this study involving animals were in accordance with the ethical standards of “Ethics Committee Acts” of Shengjing Hospital of China Medical University.

Human and animal rights

This article does not contain any studies with human performed by the any of the authors. The experimental procedures for all animals were in accordance with the Ethics Committee Acts of Shengjing Hospital of China Medical University.

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For this type of study formal consent is not required.

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Wu, N., Shen, H., Wang, Y. et al. Role of the PKCβII/JNK signaling pathway in acute glucose fluctuation-induced apoptosis of rat vascular endothelial cells. Acta Diabetol 54, 727–736 (2017). https://doi.org/10.1007/s00592-017-0999-5

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  • DOI: https://doi.org/10.1007/s00592-017-0999-5

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