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

Zhang, Hao; Wei, Jing; Xue, Rong; Wu, Jin-Dan; Zhao, Wei; Wang, Zi-Zheng; Wang, Shu-Kui; Zhou, Zheng-Xian; Song, Dan-Qing; Wang, Yue-Ming; Pan, Huai-Ning; Kong, Wei-Jia; Jiang, Jian-Dong

doi:10.1016/j.metabol.2009.07.029

« Previous Next »Metabolism - Clinical and Experimental
Volume 59, Issue 2 , Pages 285-292, February 2010

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

Hao Zhang
- Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
- These authors contributed equally to this work.
Jing Wei
- Department of Medicine, Nanjing First Hospital, Nanjing 210006, China
- These authors contributed equally to this work.
Rong Xue
- Department of Medicine, Nanjing Second Hospital, Nanjing 210003, China
- These authors contributed equally to this work.
Jin-Dan Wu
- Department of Medicine, Nanjing First Hospital, Nanjing 210006, China
Wei Zhao
- Department of Medicine, Nanjing Second Hospital, Nanjing 210003, China
Zi-Zheng Wang
- Department of Medicine, Nanjing First Hospital, Nanjing 210006, China
Shu-Kui Wang
- Department of Medicine, Nanjing First Hospital, Nanjing 210006, China
Zheng-Xian Zhou
- Department of Medicine, Nanjing Second Hospital, Nanjing 210003, China
Dan-Qing Song
- Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
Yue-Ming Wang
- Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
Huai-Ning Pan
- Department of Medicine, Nanjing First Hospital, Nanjing 210006, China
Wei-Jia Kong
- Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
- 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.
Jian-Dong Jiang
- Department of Pharmacology, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences, Beijing 100050, China
- 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.

Received 23 March 2009; accepted 28 July 2009. published online 05 October 2009.

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 A_1c, triglyceride, and insulin levels in patients with type 2 diabetes mellitus (T2DM). The FBG- and hemoglobin A_1c–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.