Basic Research
Copyright ©2008 The WJG Press and Baishideng. All rights reserved.
World J Gastroenterol. Oct 21, 2008; 14(39): 6004-6011
Published online Oct 21, 2008. doi: 10.3748/wjg.14.6004
Facilitating effects of berberine on rat pancreatic islets through modulating hepatic nuclear factor 4 alpha expression and glucokinase activity
Zhi-Quan Wang, Fu-Er Lu, San-Hua Leng, Xin-Sheng Fang, Guang Chen, Zeng-Si Wang, Li-Ping Dong, Zhong-Qing Yan
Zhi-Quan Wang, Fu-Er Lu, San-Hua Leng, Xin-Sheng Fang, Guang Chen, Zeng-Si Wang, Li-Ping Dong, Zhong-Qing Yan, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China
Author contributions: Lu FE and Leng SH designed the research; Wang ZQ, Fang XS, Chen G, Wang ZS, Dong LP and Yan ZQ performed the research; Wang ZQ and Fang XS analyzed the data; and Wang ZQ wrote the paper.
Supported by The National Natural Science Foundation of China, No. 30500685
Correspondence to: Dr. Fu-Er Lu, Institute of Integrated Traditional Chinese and Western Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, Hubei Province, China. felu@tjh.tjmu.edu.cn
Telephone: +86-27-83663237 Fax: +86-27-83663237
Received: June 23, 2008
Revised: September 20, 2008
Accepted: September 27, 2008
Published online: October 21, 2008
Abstract

AIM: To observe the effect of berberine on insulin secretion in rat pancreatic islets and to explore its possible molecular mechanism.

METHODS: Primary rat islets were isolated from male Sprague-Dawley rats by collagenase digestion and treated with different concentrations (1, 3, 10 and 30 μmol/L) of berberine or 1 μmol/L Glibenclamide (GB) for 24 h. Glucose-stimulated insulin secretion (GSIS) assay was conducted and insulin was determined by radioimmunoassay. 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed to evaluate cytotoxicity. The mRNA level of hepatic nuclear factor 4 alpha (HNF4α) was determined by reverse transcription polymerase chain reaction (RT-PCR). Indirect immunofluorescence staining and Western blot analysis were employed to detect protein expression of HNF4α in the islets. Glucokinase (GK) activity was measured by spectrophotometric method.

RESULTS: Berberine enhanced GSIS rather than basal insulin secretion dose-dependently in rat islets and showed no significant cytotoxicity on islet cells at the concentration of 10 μmol/L. Both mRNA and protein expressions of HNF4α were up-regulated by berberine in a dose-dependent manner, and GK activity was also increased accordingly. However, GB demonstrated no regulatory effects on HNF4α expression or GK activity.

CONCLUSION: Berberine can enhance GSIS in rat islets, and probably exerts the insulinotropic effect via a pathway involving HNF4α and GK, which is distinct from sulphonylureas (SUs).

Keywords: Berberine; Sulphonylureas; Hepatocyte nuclear factor 4 alpha; Glucokinase; Pancreatic islet