期刊
MOLECULAR ENDOCRINOLOGY
卷 30, 期 3, 页码 361-371出版社
ENDOCRINE SOC
DOI: 10.1210/me.2015-1213
关键词
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资金
- European Foundation for the Study of Diabetes (EFSD)
- Chinese Diabetes Society (CDS)
- Lilly Programme for Collaborative Research between China and Europe
- Natural Science Foundation of China [81102488, 81370924]
- Natural Science Foundation of Jiangsu Province [BK2011865]
- Foundation for High-Level Talent in Six Areas of Jiangsu Province [2015-YY010]
- Foundation of Jiangsu Province Administration of Traditional Chinese Medicine [LZ13066]
Diabetes is characterized by a loss and dysfunction of the beta-cell. Glucagon-like peptide 1 receptor (GLP-1R) signaling plays an important role in beta-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 beta-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 beta-cell mass and beta-cell proliferation but decreased beta-cell apoptosis were observed in puerarin-treated diabetic mice as examined by immunostaining of mice pancreatic sections. The protective effect of puerarin on beta-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 beta-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 beta-cell survival by mechanisms involving activation of GLP-1R signaling and downstream targets.
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