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dc.contributor.authorWang, Jie
dc.contributor.authorGu, Wenyi
dc.contributor.authorChen, Chen
dc.date.accessioned2019-09-10T03:03:41Z
dc.date.available2019-09-10T03:03:41Z
dc.date.issued2018
dc.identifier.issn1422-0067en_US
dc.identifier.doi10.3390/ijms19040985en_US
dc.identifier.urihttp://hdl.handle.net/10072/387165
dc.description.abstractType 2 diabetes (T2D) is a metabolic disorder characterized by beta cell dysfunction and insulin resistance in fat, muscle and liver cells. Recent studies have shown that the development of insulin resistance in pancreatic beta cell lines may contribute to beta cell dysfunction in T2D. However, there still is a lack of detailed investigations regarding the mechanisms by which insulin deficiency may contribute in diabetes. In this study, we firstly established a stable insulin receptor knockdown cell line in pancreatic beta cells INS-1 (InsRβKD cells) using anti InsRβ small hairpin RNA (InsRβ-shRNA) encoded by lentiviral vectors. The resultant InsRβKD cells demonstrated a significantly reduced expression of InsRβ as determined by real-time PCR and Western blotting analyses. Upon removing glucose from the medium, these cells exhibited a significant decrease in insulin gene expression and protein secretion in response to 20 mM glucose stimulation. In accordance with this insulin reduction, the glucose uptake efficiency as indicated by a3[H]-2-deoxy-D-glucose assay also decreased. Furthermore, InsRβKD cells showed a dramatic decrease in glucose transporter 2 (GLUT2, encoded by SLC2A2) and pancreatic duodenal homeobox (Pdx1) mRNA expression compared to the controls. These data collectively suggest that pancreatic beta cell insulin resistance contributes to the development of beta cell dysfunction by impairing pancreatic beta cell glucose sensation through the Pdx1- GLUT2 pathway. InsRβKD cells provide a good model to further investigate the mechanism of β-cell dysfunction in T2D.en_US
dc.description.peerreviewedYesen_US
dc.languageEnglishen_US
dc.publisherMDPIen_US
dc.relation.ispartofpagefrom985-1en_US
dc.relation.ispartofpageto985-13en_US
dc.relation.ispartofissue4en_US
dc.relation.ispartofjournalInternational Journal of Molecular Sciencesen_US
dc.relation.ispartofvolume19en_US
dc.subject.fieldofresearchOther Chemical Sciencesen_US
dc.subject.fieldofresearchGeneticsen_US
dc.subject.fieldofresearchOther Biological Sciencesen_US
dc.subject.fieldofresearchcode0399en_US
dc.subject.fieldofresearchcode0604en_US
dc.subject.fieldofresearchcode0699en_US
dc.subject.keywordsScience & Technologyen_US
dc.subject.keywordsLife Sciences & Biomedicineen_US
dc.subject.keywordsPhysical Sciencesen_US
dc.subject.keywordsBiochemistry & Molecular Biologyen_US
dc.subject.keywordsChemistry, Multidisciplinaryen_US
dc.titleKnocking down Insulin Receptor in Pancreatic Beta Cell lines with Lentiviral-Small Hairpin RNA Reduces Glucose-Stimulated Insulin Secretion via Decreasing the Gene Expression of Insulin, GLUT2 and Pdx1en_US
dc.typeJournal articleen_US
dc.type.descriptionC1 - Articlesen_US
dcterms.bibliographicCitationWang, J; Gu, W; Chen, C, Knocking down Insulin Receptor in Pancreatic Beta Cell lines with Lentiviral-Small Hairpin RNA Reduces Glucose-Stimulated Insulin Secretion via Decreasing the Gene Expression of Insulin, GLUT2 and Pdx1, International Journal of Molecular Sciences, 2018, 19 (4), pp. 985-1 - 985-13en_US
dcterms.dateAccepted2018-03-21
dcterms.licensehttp://creativecommons.org/licenses/by/4.0/en_US
dc.date.updated2019-09-10T02:58:03Z
dc.description.versionPublisheden_US
gro.rights.copyright© 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (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.en_US
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gro.griffith.authorChen, Chen


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