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Journal of Cellular Biochemistry

Wnt3a regulates proliferation, apoptosis and function of pancreatic NIT-1 beta cells via activation of IRS2/PI3K signaling

Authors

  • Shuyan Gui,

    1. Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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  • Dr. Gang Yuan MD, PhD,

    Corresponding author
    1. Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
    • Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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  • Lu Wang,

    1. Institute of Organ Transplantation, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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  • Lili Zhou,

    1. Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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  • Ying Xue,

    1. Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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  • Yikai Yu,

    1. Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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  • Jianhua Zhang,

    1. Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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  • Muxun Zhang,

    1. Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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  • Yan Yang,

    1. Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
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  • Dao Wen Wang MD, PhD

    Corresponding author
    1. Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China
    • Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
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  • Shuyan Gui and Gang Yuan contributed equally to this work.

  • Disclosure statement: The authors have nothing to disclose.

Abstract

Wnt-signaling pathway is implicated in pancreatic development and functional regulation of mature beta-cells. Wnt3a/Wnt pathway activation expands islet cell mass in vitro by increasing proliferation and decreasing apoptosis of beta-cells, thereby enhancing its function. However, the signaling pathways that mediate these effects remain unknown. By using a clonal beta-cell line (NIT-1), we examined the role of IRS2/PI3K in the mediation of Wnt3a-stimulated beta-cell growth. Real-time PCR and Western blot were employed to investigate the activity of Wnt/β-catenin and IRS2/PI3K signaling. Proliferation of NIT-1 cells was assessed by BrdU incorporation, and apoptosis was quantitatively determined by TUNEL and flow cytometry (FCM). Dkk1, an inhibitor of Wnt signaling, and wortmannin, an inhibitor of PI3K, were also used. Results showed that Wnt3a rapidly activated Wnt/β-catenin signaling, promoted IRS2 expression and Akt phosphorylation in NIT-1 cells. These effects were completely abrogated by Dkk1 or partially eliminated by wortmannin. Wnt3a also promoted NIT-1 cell proliferation, inhibited cytokine-induced beta-cell apoptosis, and increased insulin secretion. Both of these effects were also eliminated by Dkk1 or wortmannin. Our results demonstrated that Wnt3a regulates proliferation, apoptosis and enhances function of pancreatic NIT-1 beta cells via activation of Wnt/β-catenin signaling, involving crosstalk with IRS2/PI3K signaling, with the effect of Wnt signaling on beta-cells also being IRS2/PI3K/AKT dependent. J. Cell. Biochem. 114: 1488–1497, 2013. © 2013 Wiley Periodicals, Inc.

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