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Intermittent high glucose induces pyroptosis of rat H9C2 cardiomyocytes via sodium–glucose cotransporter 1

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Abstract

Cardiomyocyte death is an important pathogenic process in cardiac complications of diabetes. Diabetic patients often suffer glycemic variability. Pyroptosis is a form of programmed cell death triggered by inflammasomes and related with caspase-1 and gasdermin D activation. The present study was designed to examine the effects of intermittent high glucose simulating glycemic variability on the pyroptosis of cardiomyocytes in vitro. Rat H9C2 cardiomyocytes were incubated with normal glucose (NG), constant high glucose (CHG) and intermittent high glucose (IHG). Results showed that compared to CHG treatment, IHG further inhibited cell proliferation and promoted cell death of H9C2 cardiomyocytes. In addition, IHG upregulated higher levels of the expressions of inflammasome NLR family pyrin domain containing 3 (NLRP3) and adaptor protein apoptosis-associated speck-like protein containing CARD domain (ASC) and increased higher levels of activated caspase-1 and gasdermin D than CHG treatment. Moreover, the production of reactive oxygen species (ROS) and activation of NF-κB that is induced by IHG were significantly higher than that induced by CHG. Knockdown of sodium–glucose cotransporters 1 (SGLT1) in H9C2 cardiomyocytes was performed and the effects of SGLT1 on IHG-induced pyroptosis was evaluated. The results demonstrated that knockdown of SGLT1 partially reduced IHG-induced pyroptosis, ROS generation and NF-κB activation. Our results indicated that IHG is harmful to cardiomyocytes and it might be partially because of the SGLT1-depedent pyroptosis in cardiomyocytes.

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Funding

This study was funded by the National Natural Science Foundation of China (No. 81870565).

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  1. Qian Chai and Ziang Meng have contributed equally to this study.

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  1. Department of Endocrinology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Harbin, 150001, People’s Republic of China

    Qian Chai, Dexue Lu, Ziying Zhang, Meili Liu & Weihua Wu

  2. Department of Urology, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, 150001, People’s Republic of China

    Ziang Meng

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  1. Qian Chai
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Chai, Q., Meng, Z., Lu, D. et al. Intermittent high glucose induces pyroptosis of rat H9C2 cardiomyocytes via sodium–glucose cotransporter 1. Mol Cell Biochem 476, 2479–2489 (2021). https://doi.org/10.1007/s11010-021-04104-6

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