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Biomed Pharmacother. 2018 Jan;97:880-885. doi: 10.1016/j.biopha.2017.11.020. Epub 2017 Nov 7.

Cardiac apoptosis induced under high glucose condition involves activation of IGF2R signaling in H9c2 cardiomyoblasts and streptozotocin-induced diabetic rat hearts.

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Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan.
Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan.
Department of Nursing, Meiho University, Pingtung 91202, Taiwan.
School of Post-Baccalaureate Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung 404025, Taiwan.
Department of Surgery, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Department of Biotechnology, Bharathiar University, Coimbatore 641046, India.
Department of Pathology, Changhua Christian Hospital, Changhua, Taiwan; Department of Medical Technology, Jen-Teh Junior College of Medicine, Nursing and Management, Miaoli, Taiwan.
Graduate Institute of Basic Medical Science, China Medical University, Taichung 40402, Taiwan; School of Chinese Medicine, China Medical University, Taichung, Taiwan; Department of Biological Science and Technology, Asia University, Taichung 41354, Taiwan. Electronic address:


The insulin-like growth factor type 2 receptor (IGF2R) overexpression has been implicated in heart disease progression. Unregulated IGF2R signaling triggers cardiac hypertrophy, apoptosis, and cardiomyopathies. The present study investigated the role of IGF2R in cardiomyocyte apoptosis under high glucose (HG) levels and in streptozotocin (STZ) induced diabetic rat hearts. We found that IGF2 and IGF2R protein expression were highly upregulated under high glucose condition in H9c2 cells as well as in STZ induced diabetic rat hearts. Using immunoblotting and TUNEL assay, we found that elevated glucose condition induced IGF2R expression leads to activation of Gαq mediated calcineurin-dependent signaling pathway, which further leads to downstream activation and expression of cardiac hypertrophy related proteins, ANP and BNP. Further, we found that glucose-induced IGF2R expression downregulated survival protein p-Akt, p-Bad (Ser 155) and enhanced the expression of apoptosis-inducing proteins cytochrome c and cleaved Caspase-3. Our results suggested that hyperglycemic condition leads to cellular cardiomyocyte apoptosis both in vitro and in vivo models, via abnormally increased activation of the IGF2R signaling pathway.


Apoptosis; Diabetic hyperglycemic; High glucose (HG); IGF2R

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