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Puerarin Protects Pancreatic β-Cells in Obese Diabetic Mice via Activation of GLP-1R Signaling.

Authors
  • Yang, Lei1
  • Yao, Dongdong1
  • Yang, Haiyuan1
  • Wei, Yingjie1
  • Peng, Yunru1
  • Ding, Yongfang1
  • Shu, Luan1
  • 1 Affiliated Hospital of Integrated Traditional Chinese and Western Medicine (L.Y., D.Y., Y.W., Y.P., Y.D., L.S.), Nanjing University of Chinese Medicine, Nanjing, 210028 China; Key Laboratory of New Drug Delivery System of Chinese Materia Medica (L.Y., D.Y., Y.W., Y.P., Y.D., L.S.), Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, 210028 China; and Jiangsu Key Laboratory of Xenotransplantation (H.Y.), Nanjing Medical University, Nanjing, 210029 China.
Type
Published Article
Journal
Molecular Endocrinology
Publisher
The Endocrine Society
Publication Date
March 2016
Volume
30
Issue
3
Pages
361–371
Identifiers
DOI: 10.1210/me.2015-1213
PMID: 26789107
Source
Medline
License
Unknown

Abstract

Diabetes is characterized by a loss and dysfunction of the β-cell. Glucagon-like peptide 1 receptor (GLP-1R) signaling plays an important role in β-cell survival and function. It is meaningful to identify promising agents from natural products which might activate GLP-1R signaling. In this study, puerarin, a diet isoflavone, was evaluated its beneficial effects on β-cell survival and GLP-1R pathway. We showed that puerarin reduced the body weight gain, normalized blood glucose, and improved glucose tolerance in high-fat diet-induced and db/db diabetic mice. Most importantly, increased β-cell mass and β-cell proliferation but decreased β-cell apoptosis were observed in puerarin-treated diabetic mice as examined by immunostaining of mice pancreatic sections. The protective effect of puerarin on β-cell survival was confirmed in isolated mouse islets treated with high glucose. Further mechanism studies showed that the circulating level of GLP-1 in mice was unaffected by puerarin. However, puerarin enhanced GLP-1R signaling by up-regulating expressions of GLP-1R and pancreatic and duodenal homeobox 1, which subsequently led to protein kinase B (Akt) activation but forkhead box O1 inactivation, and promoted β-cell survival. The protective effect of puerarin was remarkably suppressed by Exendin(9-39), an antagonist of GLP-1R. Our study demonstrated puerarin improved glucose homeostasis in obese diabetic mice and identified a novel role of puerarin in protecting β-cell survival by mechanisms involving activation of GLP-1R signaling and downstream targets.

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