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dc.contributor.authorHuang, Xiao-Ting
dc.contributor.authorLi, Chen
dc.contributor.authorPeng, Xiang-Ping
dc.contributor.authorGuo, Jia
dc.contributor.authorYue, Shao-Jie
dc.contributor.authorLiu, Wei
dc.contributor.authorZhao, Fei-Yan
dc.contributor.authorHan, Jian-Zhong
dc.contributor.authorHuang, Yan-Hong
dc.contributor.authorYang-Li
dc.contributor.authorCheng, Qing-Mei
dc.contributor.authorZhou, Zhi-Guang
dc.contributor.authorChen, Chen
dc.contributor.authorFeng, Dan-Dan
dc.contributor.authorLuo, Zi-Qiang
dc.date.accessioned2020-02-26T23:40:04Z
dc.date.available2020-02-26T23:40:04Z
dc.date.issued2017
dc.identifier.issn2045-2322
dc.identifier.doi10.1038/srep44120
dc.identifier.urihttp://hdl.handle.net/10072/391939
dc.description.abstractIn the nervous system, excessive activation of NMDA receptors causes neuronal injury. Although activation of NMDARs has been proposed to contribute to the progress of diabetes, little is known about the effect of excessive long-term activation of NMDARs on β-cells, especially under the challenge of hyperglycemia. Here we thoroughly investigated whether endogenous glutamate aggravated β-cell dysfunction under chronic exposure to high-glucose via activation of NMDARs. The glutamate level was increased in plasma of diabetic mice or patients and in the supernatant of β-cell lines after treatment with high-glucose for 72 h. Decomposing the released glutamate improved GSIS of β-cells under chronic high-glucose exposure. Long-term treatment of β-cells with NMDA inhibited cell viability and decreased GSIS. These effects were eliminated by GluN1 knockout. The NMDAR antagonist MK-801 or GluN1 knockout prevented high-glucose-induced dysfunction in β-cells. MK-801 also decreased the expression of pro-inflammatory cytokines, and inhibited I-κB degradation, ROS generation and NLRP3 inflammasome expression in β-cells exposed to high-glucose. Furthermore, another NMDAR antagonist, Memantine, improved β-cells function in diabetic mice. Taken together, these findings indicate that an increase of glutamate may contribute to the development of diabetes through excessive activation of NMDARs in β-cells, accelerating β-cells dysfunction and apoptosis induced by hyperglycemia.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherNature Publishing Group
dc.relation.ispartofissue1
dc.relation.ispartofjournalScientific Reports
dc.relation.ispartofvolume7
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchOther Physical Sciences
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode0299
dc.subject.keywordsScience & Technology
dc.subject.keywordsMultidisciplinary Sciences
dc.subject.keywordsScience & Technology - Other Topics
dc.subject.keywordsTYPE-2
dc.subject.keywordsGLUCOTOXICITY
dc.titleAn excessive increase in glutamate contributes to glucose-toxicity in beta-cells via activation of pancreatic NMDA receptors in rodent diabetes
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationHuang, X-T; Li, C; Peng, X-P; Guo, J; Yue, S-J; Liu, W; Zhao, F-Y; Han, J-Z; Huang, Y-H; Yang-Li; Cheng, Q-M; Zhou, Z-G; Chen, C; Feng, D-D; Luo, Z-Q, An excessive increase in glutamate contributes to glucose-toxicity in beta-cells via activation of pancreatic NMDA receptors in rodent diabetes, Scientific Reports, 2017, 7 (1)
dcterms.dateAccepted2017-02-06
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2020-02-25T01:39:05Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© The Author(s) 2017. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.
gro.hasfulltextFull Text
gro.griffith.authorChen, Chen


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