title: Berberine inhibits mouse insulin gene promoter through activation of AMP activated protein kinase and may exert beneficial effect on pancreatic β-cell.
abstract: 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 β-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.
authors.affiliation: State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Xiannongtan Street, Beijing 100050, China.
authors.forename: Ning
authors.initials: N
authors.lastname: Shen
authors.forename: Yi
authors.initials: Y
authors.lastname: Huan
authors.forename: Zhu-fang
authors.initials: ZF
authors.lastname: Shen
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001599:Berberine / Q000494:pharmacology* / Q000627:therapeutic use; D001786:Blood Glucose / Q000378:metabolism; D002460:Cell Line; D059305:Diet, High-Fat / Q000009:adverse effects; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D018149:Glucose Intolerance / Q000188:drug therapy / Q000209:etiology / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D007328:Insulin / Q000235:genetics* / Q000378:metabolism; D007333:Insulin Resistance / Q000235:genetics; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D051379:Mice; D011401:Promoter Regions, Genetic / Q000187:drug effects* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D001786:Blood Glucose; C561967:Ins2 protein, mouse; D007328:Insulin; D012333:RNA, Messenger; D001599:Berberine; D055372:AMP-Activated Protein Kinases