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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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Received: 16 January 2014; in revised form: 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 which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

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.

AMA Style

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. International Journal of Molecular Sciences. 2014; 15(5):9016-9035.

Chicago/Turabian Style

Wang, Hai-Lian; Li, Chun-Yang; Zhang, Bin; Liu, Yuan-De; Lu, Bang-Min; Shi, Zheng; An, Na; Zhao, Liang-Kai; Zhang, Jing-Jing; Bao, Jin-Ku; Wang, Yi. 2014. "Mangiferin Facilitates Islet Regeneration and β-Cell Proliferation through Upregulation of Cell Cycle and β-Cell Regeneration Regulators." Int. J. Mol. Sci. 15, no. 5: 9016-9035.



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