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Galectin-3 impairs calcium transients and β-cell function

Author

Listed:
  • Qian Jiang

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Diabetes Research Center of Chinese Academy of Medical Sciences
    CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis)

  • Qijin Zhao

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Diabetes Research Center of Chinese Academy of Medical Sciences
    CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis)

  • Yibing Chen

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Diabetes Research Center of Chinese Academy of Medical Sciences
    CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis)

  • Chunxiao Ma

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Diabetes Research Center of Chinese Academy of Medical Sciences
    CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis)

  • Xiaohong Peng

    (Peking University
    Peking University)

  • Xi Wu

    (Peking University
    Peking University)

  • Xingfeng Liu

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Diabetes Research Center of Chinese Academy of Medical Sciences
    CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis)

  • Ruoran Wang

    (Zhejiang University)

  • Shaocong Hou

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Diabetes Research Center of Chinese Academy of Medical Sciences
    CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis)

  • Lijuan Kong

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Diabetes Research Center of Chinese Academy of Medical Sciences
    CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis)

  • Yanjun Wan

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Diabetes Research Center of Chinese Academy of Medical Sciences
    CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis)

  • Shusen Wang

    (Nankai University)

  • Zhuo-Xian Meng

    (Zhejiang University)

  • Bing Cui

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Diabetes Research Center of Chinese Academy of Medical Sciences
    CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis)

  • Liangyi Chen

    (Peking University
    Peking University
    Peking University)

  • Pingping Li

    (Chinese Academy of Medical Sciences and Peking Union Medical College
    Diabetes Research Center of Chinese Academy of Medical Sciences
    CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis)

Abstract

In diabetes, macrophages and inflammation are increased in the islets, along with β-cell dysfunction. Here, we demonstrate that galectin-3 (Gal3), mainly produced and secreted by macrophages, is elevated in islets from both high-fat diet (HFD)-fed and diabetic db/db mice. Gal3 acutely reduces glucose-stimulated insulin secretion (GSIS) in β-cell lines and primary islets in mice and humans. Importantly, Gal3 binds to calcium voltage-gated channel auxiliary subunit gamma 1 (CACNG1) and inhibits calcium influx via the cytomembrane and subsequent GSIS. β-Cell CACNG1 deficiency phenocopies Gal3 treatment. Inhibition of Gal3 through either genetic or pharmacologic loss of function improves GSIS and glucose homeostasis in both HFD-fed and db/db mice. All animal findings are applicable to male mice. Here we show a role of Gal3 in pancreatic β-cell dysfunction, and Gal3 could be a therapeutic target for the treatment of type 2 diabetes.

Suggested Citation

  • Qian Jiang & Qijin Zhao & Yibing Chen & Chunxiao Ma & Xiaohong Peng & Xi Wu & Xingfeng Liu & Ruoran Wang & Shaocong Hou & Lijuan Kong & Yanjun Wan & Shusen Wang & Zhuo-Xian Meng & Bing Cui & Liangyi C, 2024. "Galectin-3 impairs calcium transients and β-cell function," Nature Communications, Nature, vol. 15(1), pages 1-17, December.
    • Handle: RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-47959-1
    DOI: 10.1038/s41467-024-47959-1
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