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Int J Mol Sci. 2014 May 20;15(5):9016-35. doi: 10.3390/ijms15059016.

Mangiferin facilitates islet regeneration and β-cell proliferation through upregulation of cell cycle and β-cell regeneration regulators.

Author information

  • 1School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. hailianwang322@hotmail.com.
  • 2School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. vivian-goldenblue@163.com.
  • 3School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. binzhang@163.com.
  • 4Department of Pharmacy, 91889 Military Hospital, Zhanjiang 524001, China. yuandeliu@126.com.
  • 5School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. lubangmin@126.com.
  • 6School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. drshiz1002@hotmail.com.
  • 7School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. anna1208lucky@gmail.com.
  • 8School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. kailiangzhao@163.com.
  • 9Institute of Neurology Science, Guangdong Medical University Affiliated Hospital, Zhanjiang 524001, China. jingjingzhang12@163.com.
  • 10School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. jinkubao@yahoo.com.
  • 11Department of Pharmacy, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu 610072, China. w_yi@yahoo.com.

Abstract

Mangiferin, a xanthonoid found in plants including mangoes and iris unguicularis, was suggested in previous studies to have anti-hyperglycemic function, though the underlying mechanisms are largely unknown. This study was designed to determine the therapeutic effect of mangiferin by the regeneration of β-cells in mice following 70% partial pancreatectomy (PPx), and to explore the mechanisms of mangiferin-induced β-cell proliferation. For this purpose, adult C57BL/6J mice after 7-14 days post-PPx, or a sham operation were subjected to mangiferin (30 and 90 mg/kg body weight) or control solvent injection. Mangiferin-treated mice exhibited an improved glycemia and glucose tolerance, increased serum insulin levels, enhanced β-cell hyperplasia, elevated β-cell proliferation and reduced β-cell apoptosis. Further dissection at the molecular level showed several key regulators of cell cycle, such as cyclin D1, D2 and cyclin-dependent kinase 4 (Cdk4) were significantly up-regulated in mangiferin-treated mice. In addition, critical genes related to β-cell regeneration, such as pancreatic and duodenal homeobox 1 (PDX-1), neurogenin 3 (Ngn3), glucose transporter 2 (GLUT-2), Forkhead box protein O1 (Foxo-1), and glucokinase (GCK), were found to be promoted by mangiferin at both the mRNA and protein expression level. Thus, mangiferin administration markedly facilitates β-cell proliferation and islet regeneration, likely by regulating essential genes in the cell cycle and the process of islet regeneration. These effects therefore suggest that mangiferin bears a therapeutic potential in preventing and/or treating the diabetes.

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