Mangiferin facilitates islet regeneration and β-cell proliferation through upregulation of cell cycle and β-cell regeneration regulators.
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.
School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. hailianwang322@hotmail.com.
Hai-Lian
HL
Wang
School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. vivian-goldenblue@163.com.
Chun-Yang
CY
Li
School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. binzhang@163.com.
Bin
B
Zhang
Department of Pharmacy, 91889 Military Hospital, Zhanjiang 524001, China. yuandeliu@126.com.
Yuan-De
YD
Liu
School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. lubangmin@126.com.
Bang-Min
BM
Lu
School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. drshiz1002@hotmail.com.
Zheng
Z
Shi
School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. anna1208lucky@gmail.com.
Na
N
An
School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. kailiangzhao@163.com.
Liang-Kai
LK
Zhao
Institute of Neurology Science, Guangdong Medical University Affiliated Hospital, Zhanjiang 524001, China. jingjingzhang12@163.com.
Jing-Jing
JJ
Zhang
School of Life Sciences & Key Laboratory of Bio-Resources, Ministry of Education, Sichuan University, Chengdu 610064, China. jinkubao@yahoo.com.
Jin-Ku
JK
Bao
Department of Pharmacy, Sichuan Academy of Medical Science & Sichuan Provincial People's Hospital, Chengdu 610072, China. w_yi@yahoo.com.
Yi
Y
Wang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D056742:Cyclin D2 / Q000235:genetics / Q000378:metabolism; D051358:Cyclin-Dependent Kinase 4 / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000097:blood; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000502:physiology / Q000601:surgery; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012038:Regeneration / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects*; D044004:Xanthones / Q000494:pharmacology*
D056742:Cyclin D2; D007328:Insulin; D044004:Xanthones; D019938:Cyclin D1; C013592:mangiferin; D051358:Cyclin-Dependent Kinase 4; D005947:Glucose