Galectin-3 impairs calcium transients and β-cell function

  • Nat Commun. 2024 May 1;15(1):3682. doi: 10.1038/s41467-024-47959-1.
Qian Jiang  #  1  2  3 ,  Qijin Zhao  #  1  2  3 ,  Yibing Chen  #  1  2  3 ,  Chunxiao Ma  #  1  2  3 ,  Xiaohong Peng  4  5 ,  Xi Wu  6  7 ,  Xingfeng Liu  1  2  3 ,  Ruoran Wang  8 ,  Shaocong Hou  1  2  3 ,  Lijuan Kong  1  2  3 ,  Yanjun Wan  1  2  3 ,  Shusen Wang  9 ,  Zhuo-Xian Meng  8 ,  Bing Cui  1  2  3 ,  Liangyi Chen  4  5  7 ,  Pingping Li  10  11  12
Affiliations
  • 1. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China.
  • 2. Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, 100050, China.
  • 3. CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis, Beijing, 100050, China.
  • 4. College of Future Technology, Institute of Molecular Medicine, National Biomedical Imaging Center, Peking University, Beijing, 100871, China.
  • 5. Beijing Key Laboratory of Cardiometabolic Molecular Medicine, Peking University, Beijing, 100871, China.
  • 6. State Key Laboratory of Membrane Biology, College of Future Technology, Institute of Molecular Medicine, Peking University, Beijing, 100871, China.
  • 7. Peking-Tsinghua Center for Life Sciences, Peking University, Beijing, 100871, China.
  • 8. School of Basic Medical Sciences, Zhejiang University, Hangzhou, Zhejiang, China.
  • 9. Organ Transplant Center, Tianjin First Central Hospital, Nankai University, Tianjin, 300192, China.
  • 10. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100050, China. [email protected].
  • 11. Diabetes Research Center of Chinese Academy of Medical Sciences, Beijing, 100050, China. [email protected].
  • 12. CAMS Key Laboratory of Molecular Mechanism and Target Discovery of Metabolic Disorder and Tumorigenesis, Beijing, 100050, China. [email protected].
  • # Contributed equally.
PMID: 38693121 DOI: 10.1038/s41467-024-47959-1
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.

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