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Cardiac-derived adiponectin induced by long-term insulin treatment ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic mice via AMPK signaling

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Abstract

Type 1 diabetes (T1DM) portends poor prognosis concerning ischemic heart disease. Adiponectin (APN), an adipocytokine possessing insulin sensitizing and metabolic regulatory effects, has been recognized as a potent cardioprotective molecule. However, the relationship between APN and T1DM remains controversial and the role of cardiac-derived APN in T1DM is unclear. This study is aimed to investigate the dynamic change of both plasma and cardiac-derived APN expressions in T1DM, and the particular role of cardiac-derived APN in T1DM against myocardial ischemia/reperfusion (MI/R) injury. T1DM was established via intraperitoneal injection of streptozocin and followed by twice-daily subcutaneous injection of insulin or vehicle for 14 days. Non-diabetic mice of wild type and APN knockout were subjected to insulin or vehicle injection. MI/R was induced in Langendorff-perfused hearts. Compared to non-diabetic mice, plasma APN levels of diabetic mice significantly increased at 7 days, and slightly decreased at 14 days, while cardiac-derived APN levels gradually decreased over time. The MI/R injury measured as infarct size and cardiomyocyte apoptosis nearly doubled in diabetic mice. 14 days of insulin treatment increased both plasma and cardiac-derived APN levels in diabetic mice and attenuated myocardial injury via increasing AMPK phosphorylation in T1DM, which was partly reversed by Compound C (an AMPK inhibitor). Moreover, APN deficiency aggravated MI/R injury and partly abolished the protective effect of insulin treatment against MI/R injury, which was associated with decreased AMPK phosphorylation. The results suggest that cardiac-derived APN stimulated by long-term insulin treatment in T1DM exerts cardioprotection against MI/R injury via myocardial AMPK activation.

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Acknowledgments

Supported by the grants from the National Natural Science Foundation of China Nos. 81225001 (L.T.), 81070676 (L.T.), 30700255 (Y.Q.), 81070951 (Y.Q.) and 81270330 (H.Z.), National 863 Project of China 2009AA02Z104 (L.T.), and Subject Boosting Project of Xijing Hospital XJZT08Z02 (L.T.).

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None declared.

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Authors and Affiliations

  1. Department of Cardiology, Xijing Hospital, Fourth Military Medical University, 15 Changlexi Road, Xi’an, 710032, China

    Haifeng Pei, Xiaoyan Lu, Qiujun Yu, Kun Lian, Peilin Liu, Wenjun Yan, Jingyi Liu, Yanzhuo Ma, Yi Liu, Chengxiang Li, Weijie Li & Ling Tao

  2. Department of Neurosurgery, Xijing Hospital, Fourth Military Medical University, Xi’an, 710032, China

    Yan Qu

  3. Center of Teaching Experiment, School of Basic Medical Science, Fourth Military Medical University, 169 Changlexi Road, Xi’an, 710032, China

    Haifeng Zhang

  4. Department of Emergency Medicine, Thomas Jefferson University Hospital, Philadelphia, PA, 19107, USA

    Wayne Bond Lau

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  1. Haifeng Pei
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  2. Yan Qu
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  3. Xiaoyan Lu
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  13. Wayne Bond Lau
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  14. Haifeng Zhang
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  15. Ling Tao
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Correspondence to Haifeng Zhang or Ling Tao.

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H. Pei, Y. Qu, and X. Lu contributed equally to this work

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Pei, H., Qu, Y., Lu, X. et al. Cardiac-derived adiponectin induced by long-term insulin treatment ameliorates myocardial ischemia/reperfusion injury in type 1 diabetic mice via AMPK signaling. Basic Res Cardiol 108, 322 (2013). https://doi.org/10.1007/s00395-012-0322-0

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