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Int. J. Mol. Sci. 2014, 15(5), 9016-9035; doi:10.3390/ijms15059016
Article

Mangiferin Facilitates Islet Regeneration and β-Cell Proliferation through Upregulation of Cell Cycle and β-Cell Regeneration Regulators

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1,*  and 5,6,*
1 School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China 2 Institute of Organ Transplantation, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu 610072, China 3 Department of Pharmacy, 91889 Military Hospital, Zhanjiang 524001, China 4 Institute of Neurology Science, Guangdong Medical University Affiliated Hospital, Zhanjiang 524001, China 5 Department of Pharmacy, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu 610072, China 6 Center for Perinatal Research, Nationwide Children's Hospital, Columbus, OH 43205, USA These authors contributed equally to this work.
* Authors to whom correspondence should be addressed.
Received: 16 January 2014 / Revised: 21 April 2014 / Accepted: 24 April 2014 / Published: 20 May 2014
(This article belongs to the Special Issue Nutritional Control of Metabolism)
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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.
Keywords: islet regeneration; partial pancreatectomy; mangiferin; cell cycle; β-cell islet regeneration; partial pancreatectomy; mangiferin; cell cycle; β-cell
This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).
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Wang, H.-L.; Li, C.-Y.; Zhang, B.; Liu, Y.-D.; Lu, B.-M.; Shi, Z.; An, N.; Zhao, L.-K.; Zhang, J.-J.; Bao, J.-K.; Wang, Y. Mangiferin Facilitates Islet Regeneration and β-Cell Proliferation through Upregulation of Cell Cycle and β-Cell Regeneration Regulators. Int. J. Mol. Sci. 2014, 15, 9016-9035.

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