期刊
EUROPEAN JOURNAL OF PHARMACOLOGY
卷 694, 期 1-3, 页码 120-126出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.ejphar.2012.07.052
关键词
Berberine; beta-cell; AMP activated protein kinase; Insulin
资金
- National Nonprofit Institute Research Grant of CAMS-IMM [2010ZD05]
- Key Project of the National Eleventh-Five Year Research Program of China
- National S&T Major Special Project on Major New Drug Innovation [2009ZX09303-003]
Berberine is one of the main alkaloids of Rhizoma coptidis, proven to have anti-diabetic potentials through activation of AMP activated protein kinase (AMPK) in liver and muscle. However, the role of berberine on the insulin gene is unknown. Therefore, the effect of berberine on insulin gene transcription was investigated in the present study. Reporter gene assays were used in the mouse beta-cell line NIT-1 to test the effect of berberine on the promoter of mouse insulin gene Ins2. The mRNA and protein levels of insulin were also detected. Diet induced glucose intolerant mice were used to explore the effect of berberine on blood glucose homeostasis and insulin resistance in vivo. The insulin content in islet was semi-quantified by an image analysis software in the immunohistochemistry sections. The results revealed that berberine caused a reversible concentration-dependent inhibition of insulin gene transcription in NIT-1 cells which showed a significant difference from the long term used AMPK activator metformin. Such inhibition on insulin promoter resulted in the reduction of mRNA and protein of insulin. Furthermore, the inhibition of insulin promoter was totally abolished by AMPK inhibitor Compound C. Berberine significantly improved insulin resistance and glucose intolerance of mice. Likewise, insulin content in islets of berberine treated mice was also decreased. Thus, the insulin gene represents a novel target of AMPK that may contribute to the action of berberine in type 2 diabetes mellitus. (C) 2012 Elsevier B.V. All rights reserved.
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