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Article: Increased basal insulin secretion in Pdzd2-deficient mice

TitleIncreased basal insulin secretion in Pdzd2-deficient mice
Authors
KeywordsGene-trap mutagenesis
Glucose-stimulated insulin secretion
INS-1E
KATP channel
Pdzd2
Issue Date2010
PublisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/mce
Citation
Molecular And Cellular Endocrinology, 2010, v. 315 n. 1-2, p. 263-270 How to Cite?
AbstractExpression of the multi-PDZ protein Pdzd2 (PDZ domain-containing protein 2) is enriched in pancreatic islet β cells, but not in exocrine or α cells, suggesting a role for Pdzd2 in the regulation of pancreatic β-cell function. To explore the in vivo function of Pdzd2, Pdzd2-deficient mice were generated. Homozygous Pdzd2 mutant mice were viable and their gross morphology appeared normal. Interestingly, Pdzd2-deficient mice showed enhanced glucose tolerance in intraperitoneal glucose tolerance tests and their plasma insulin levels indicated increased basal insulin secretion after fasting. Moreover, insulin release from mutant pancreatic islets was found to be twofold higher than from normal islets. To verify the functional defect in vitro, Pdzd2 was depleted in INS-1E cells using two siRNA duplexes. Pdzd2-depleted INS-1E cells also displayed increased insulin secretion at low concentrations of glucose. Our results provide the first evidence that Pdzd2 is required for normal regulation of basal insulin secretion. © 2009 Elsevier Ireland Ltd. All rights reserved.
Persistent Identifierhttp://hdl.handle.net/10722/68336
ISSN
2015 Impact Factor: 3.859
2015 SCImago Journal Rankings: 2.116
ISI Accession Number ID
Funding AgencyGrant Number
Research Grants Council, HKSAR, China
University Grants Committee of the University of Hong KongHKU 7474/04M
AoE/M-04/04
Funding Information:

This work was supported by grants from the Research Grants Council, HKSAR, China and the University Grants Committee of the University of Hong Kong awarded to K.-M. Yao (HKU 7474/04M and Small Project Fund) and K. Cheah (AoE/M-04/04). We thank S. Fu, W. Chan (Transgenic Core Facility, The University of Hong Kong) and S. Tsang for ES cell culture, blastocyte injections and animal husbandry, and Y. Wang, J. Chan and W.-Y. Leung for their help in various analyses. We are grateful to M. K. Thomas, K. Chan and J. C. Y. Chan for their critical review of this manuscript.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorTsang, SWen_HK
dc.contributor.authorShao, Den_HK
dc.contributor.authorCheah, KSEen_HK
dc.contributor.authorOkuse, Ken_HK
dc.contributor.authorLeung, PSen_HK
dc.contributor.authorYao, KMen_HK
dc.date.accessioned2010-09-06T06:03:37Z-
dc.date.available2010-09-06T06:03:37Z-
dc.date.issued2010en_HK
dc.identifier.citationMolecular And Cellular Endocrinology, 2010, v. 315 n. 1-2, p. 263-270en_HK
dc.identifier.issn0303-7207en_HK
dc.identifier.urihttp://hdl.handle.net/10722/68336-
dc.description.abstractExpression of the multi-PDZ protein Pdzd2 (PDZ domain-containing protein 2) is enriched in pancreatic islet β cells, but not in exocrine or α cells, suggesting a role for Pdzd2 in the regulation of pancreatic β-cell function. To explore the in vivo function of Pdzd2, Pdzd2-deficient mice were generated. Homozygous Pdzd2 mutant mice were viable and their gross morphology appeared normal. Interestingly, Pdzd2-deficient mice showed enhanced glucose tolerance in intraperitoneal glucose tolerance tests and their plasma insulin levels indicated increased basal insulin secretion after fasting. Moreover, insulin release from mutant pancreatic islets was found to be twofold higher than from normal islets. To verify the functional defect in vitro, Pdzd2 was depleted in INS-1E cells using two siRNA duplexes. Pdzd2-depleted INS-1E cells also displayed increased insulin secretion at low concentrations of glucose. Our results provide the first evidence that Pdzd2 is required for normal regulation of basal insulin secretion. © 2009 Elsevier Ireland Ltd. All rights reserved.en_HK
dc.languageengen_HK
dc.publisherElsevier Ireland Ltd. The Journal's web site is located at http://www.elsevier.com/locate/mceen_HK
dc.relation.ispartofMolecular and Cellular Endocrinologyen_HK
dc.rightsMolecular and Cellular Endocrinology. Copyright © Elsevier Ireland Ltd.en_HK
dc.rightsCreative Commons: Attribution 3.0 Hong Kong License-
dc.subjectGene-trap mutagenesisen_HK
dc.subjectGlucose-stimulated insulin secretionen_HK
dc.subjectINS-1Een_HK
dc.subjectKATP channelen_HK
dc.subjectPdzd2en_HK
dc.subject.meshBlood Glucose - metabolism-
dc.subject.meshInsulin - blood - secretion-
dc.subject.meshInsulin-Secreting Cells - cytology - metabolism-
dc.subject.meshMice, Knockout-
dc.subject.meshNerve Tissue Proteins - genetics - metabolism-
dc.titleIncreased basal insulin secretion in Pdzd2-deficient miceen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0303-7207&volume=315&issue=1-2&spage=263&epage=270&date=2010&atitle=Increased+basal+insulin+secretion+in+Pdzd2-deficient+miceen_HK
dc.identifier.emailCheah, KSE:hrmbdkc@hku.hken_HK
dc.identifier.emailYao, KM:kmyao@hku.hken_HK
dc.identifier.authorityCheah, KSE=rp00342en_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.description.naturepostprint-
dc.identifier.doi10.1016/j.mce.2009.11.007en_HK
dc.identifier.pmid19932150-
dc.identifier.scopuseid_2-s2.0-71849102910en_HK
dc.identifier.hkuros169427en_HK
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-71849102910&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume315en_HK
dc.identifier.issue1-2en_HK
dc.identifier.spage263en_HK
dc.identifier.epage270en_HK
dc.identifier.eissn1872-8057-
dc.identifier.isiWOS:000274608900034-
dc.publisher.placeIrelanden_HK
dc.relation.projectDevelopmental genomics and skeletal research-
dc.relation.projectInvestigating the functional involvement of PDZD2 in the regulation of pancreatic beta cell gene expression and function-
dc.identifier.scopusauthoridTsang, SW=8050597200en_HK
dc.identifier.scopusauthoridShao, D=7006765448en_HK
dc.identifier.scopusauthoridCheah, KSE=35387746200en_HK
dc.identifier.scopusauthoridOkuse, K=6603069995en_HK
dc.identifier.scopusauthoridLeung, PS=7401748938en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK
dc.identifier.citeulike6197372-

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