title: Puerarin Protects Pancreatic β-Cells in Obese Diabetic Mice via Activation of GLP-1R Signaling.
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.
authors.affiliation: 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.
authors.forename: Lei
authors.initials: L
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Dongdong
authors.initials: D
authors.lastname: Yao
authors.affiliation: 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.
authors.forename: Haiyuan
authors.initials: H
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Wei
authors.affiliation: 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.
authors.forename: Yunru
authors.initials: Y
authors.lastname: Peng
authors.affiliation: 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.
authors.forename: Yongfang
authors.initials: Y
authors.lastname: Ding
authors.affiliation: 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.
authors.forename: Luan
authors.initials: L
authors.lastname: Shu
mesh_terms: D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D003921:Diabetes Mellitus, Experimental / Q000473:pathology*; D059305:Diet, High-Fat; D052216:Glucagon-Like Peptide 1 / Q000378:metabolism; D000067757:Glucagon-Like Peptide-1 Receptor / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D006943:Hyperglycemia / Q000150:complications; D050417:Insulin-Secreting Cells / Q000378:metabolism* / Q000473:pathology*; D007529:Isoflavones / Q000737:chemistry / Q000494:pharmacology*; D050356:Lipid Metabolism / Q000187:drug effects; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000067757:Glucagon-Like Peptide-1 Receptor; D007529:Isoflavones; D052216:Glucagon-Like Peptide 1; D005947:Glucose; C033607:puerarin