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dc.contributor.authorYang, Jin-Kui
dc.contributor.authorLu, Jing
dc.contributor.authorYuan, Sha-Sha
dc.contributor.authorAsan
dc.contributor.authorCao, Xi
dc.contributor.authorQiu, Hai-Yan
dc.contributor.authorShi, Ting-Ting
dc.contributor.authorYang, Fang-Yuan
dc.contributor.authorLi, Qian
dc.contributor.authorLiu, Cui-Ping
dc.contributor.authorWu, Qian
dc.contributor.authorWang, Yu-Hui
dc.contributor.authorHuang, Hai-Xia
dc.contributor.authorKayoumu, Abudurexiti
dc.contributor.authorFeng, Jian-Ping
dc.contributor.authorXie, Rong-Rong
dc.contributor.authorZhu, Xiao-Rong
dc.contributor.authorLiu, Chang
dc.contributor.authorYang, Guang-Ran
dc.contributor.authorZhang, Ming-Rong
dc.contributor.authorXie, Chun-Lan
dc.contributor.authorChen, Chen
dc.contributor.authorZhang, Bo
dc.contributor.authorLiu, George
dc.contributor.authorZhang, Xiu-Qing
dc.contributor.authorXu, Aimin
dc.date.accessioned2019-09-09T04:51:58Z
dc.date.available2019-09-09T04:51:58Z
dc.date.issued2018
dc.identifier.issn2211-1247
dc.identifier.doi10.1016/j.celrep.2018.12.005
dc.identifier.urihttp://hdl.handle.net/10072/387085
dc.description.abstractGlucose-stimulated insulin secretion from islet β cells is mediated by K ATP channels. However, the role of non-K ATP K + channels in insulin secretion is largely unknown. Here, we show that a non-K ATP K + channel, KCNH6, plays a key role in insulin secretion and glucose hemostasis in humans and mice. KCNH6 p.P235L heterozygous mutation co-separated with diabetes in a four-generation pedigree. Kcnh6 knockout (KO) or Kcnh6 p.P235L knockin (KI) mice had a phenotype characterized by changing from hypoglycemia with hyperinsulinemia to hyperglycemia with insulin deficiency. Islets from the young KO mice had increased intracellular calcium concentration and increased insulin secretion. However, islets from the adult KO mice not only had increased intracellular calcium levels but also had remarkable ER stress and apoptosis, associated with loss of β cell mass and decreased insulin secretion. Therefore, dysfunction of KCNH6 causes overstimulation of insulin secretion in the short term and β cell failure in the long term.
dc.description.peerreviewedYes
dc.languageEnglish
dc.language.isoeng
dc.publisherCell Press
dc.relation.ispartofpagefrom3800
dc.relation.ispartofpageto3810
dc.relation.ispartofissue13
dc.relation.ispartofjournalCell Reposrts
dc.relation.ispartofvolume25
dc.subject.fieldofresearchBiochemistry and Cell Biology
dc.subject.fieldofresearchMedical Physiology
dc.subject.fieldofresearchcode0601
dc.subject.fieldofresearchcode1116
dc.subject.keywordsScience & Technology
dc.subject.keywordsLife Sciences & Biomedicine
dc.subject.keywordsCell Biology
dc.subject.keywordsPANCREATIC BETA-CELLS
dc.subject.keywordsPOTASSIUM CHANNEL
dc.titleFrom Hyper- to Hypoinsulinemia and Diabetes: Effect of KCNH6 on Insulin Secretion
dc.typeJournal article
dc.type.descriptionC1 - Articles
dcterms.bibliographicCitationYang, J-K; Lu, J; Yuan, S-S; Asan; Cao, X; Qiu, H-Y; Shi, T-T; Yang, F-Y; Li, Q; Liu, C-P; Wu, Q; Wang, Y-H; Huang, H-X; Kayoumu, A; Feng, J-P; Xie, R-R; Zhu, X-R; Liu, C; Yang, G-R; Zhang, M-R; Xie, C-L; Chen, C; Zhang, B; Liu, G; Zhang, X-Q; Xu, A, From Hyper- to Hypoinsulinemia and Diabetes: Effect of KCNH6 on Insulin Secretion, Cell Reposrts, 2018, 25 (13), pp. 3800-+
dcterms.dateAccepted2018-11-30
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/
dc.date.updated2019-09-09T04:48:28Z
dc.description.versionVersion of Record (VoR)
gro.rights.copyright© 2018 The Author(s).This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/) which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
gro.hasfulltextFull Text
gro.griffith.authorChen, Chen


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