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Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin receptor expression

  • Author Footnotes
    1 These authors contributed equally to this work.
    Hao Zhang
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Jing Wei
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Medicine, Nanjing First Hospital, Nanjing 210006, China
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  • Author Footnotes
    1 These authors contributed equally to this work.
    Rong Xue
    Footnotes
    1 These authors contributed equally to this work.
    Affiliations
    Department of Medicine, Nanjing Second Hospital, Nanjing 210003, China
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  • Jin-Dan Wu
    Affiliations
    Department of Medicine, Nanjing First Hospital, Nanjing 210006, China
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  • Wei Zhao
    Affiliations
    Department of Medicine, Nanjing Second Hospital, Nanjing 210003, China
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  • Zi-Zheng Wang
    Affiliations
    Department of Medicine, Nanjing First Hospital, Nanjing 210006, China
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  • Shu-Kui Wang
    Affiliations
    Department of Medicine, Nanjing First Hospital, Nanjing 210006, China
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  • Zheng-Xian Zhou
    Affiliations
    Department of Medicine, Nanjing Second Hospital, Nanjing 210003, China
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  • Dan-Qing Song
    Affiliations
    Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
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  • Yue-Ming Wang
    Affiliations
    Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
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  • Huai-Ning Pan
    Affiliations
    Department of Medicine, Nanjing First Hospital, Nanjing 210006, China
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  • Wei-Jia Kong
    Correspondence
    Corresponding authors. Jian-Dong Jiang is to be contacted at Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China. Tel.: +86 10 63188423; fax: +86 10 63017302. Wei-Jia Kong, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China. Tel.: +86 10 63167255; fax: +86 10 63017302.
    Affiliations
    Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
    Search for articles by this author
  • Jian-Dong Jiang
    Correspondence
    Corresponding authors. Jian-Dong Jiang is to be contacted at Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China. Tel.: +86 10 63188423; fax: +86 10 63017302. Wei-Jia Kong, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China. Tel.: +86 10 63167255; fax: +86 10 63017302.
    Affiliations
    Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
    Search for articles by this author
  • Author Footnotes
    1 These authors contributed equally to this work.
Published:October 05, 2009DOI:https://doi.org/10.1016/j.metabol.2009.07.029

      Abstract

      Our previous work demonstrated that berberine (BBR) increases insulin receptor (InsR) expression and improves glucose utility both in vitro and in animal models. Here, we study the InsR–up-regulating and glucose-lowering activities of BBR in humans. Our results showed that BBR increased InsR messenger RNA and protein expression in a variety of human cell lines, including CEM, HCT-116, SW1990, HT1080, 293T, and hepatitis B virus–transfected human liver cells. Accordingly, insulin-stimulated phosphorylations of InsR β-subunit and Akt were increased after BBR treatment in cultured cells. In the clinical study, BBR significantly lowered fasting blood glucose (FBG), hemoglobin A1c, triglyceride, and insulin levels in patients with type 2 diabetes mellitus (T2DM). The FBG- and hemoglobin A1c–lowering efficacies of BBR were similar to those of metformin and rosiglitazone. In the BBR-treated patients, the percentages of peripheral blood lymphocytes that express InsR were significantly elevated after therapy. Berberine also lowered FBG effectively in chronic hepatitis B and hepatitis C patients with T2DM or impaired fasting glucose. Liver function was improved greatly in these patients by showing reduction of liver enzymes. Our results confirmed the activity of BBR on InsR in humans and its relationship with the glucose-lowering effect. Together with our previous report, we strongly suggest BBR as an ideal medicine for T2DM with a mechanism different from metformin and rosiglitazone.
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