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Article: Targeted inactivation of Kinesin-1 in pancreatic β-cells in vivo leads to insulin secretory deficiency

TitleTargeted inactivation of Kinesin-1 in pancreatic β-cells in vivo leads to insulin secretory deficiency
Authors
Issue Date2011
PublisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/
Citation
Diabetes, 2011, v. 60 n. 1, p. 320-330 How to Cite?
AbstractOBJECTIVE: Suppression of Kinesin-1 by antisense oligonucleotides, or overexpression of dominant-negative acting kinesin heavy chain, has been reported to affect the sustained phase of glucose-stimulated insulin secretion in β-cells in vitro. In this study, we examined the in vivo physiological role of Kinesin-1 in β-cell development and function. RESEARCH DESIGN AND METHODS: A Cre-LoxP strategy was used to generate conditional knockout mice in which the Kif5b gene is specifically inactivated in pancreatic β-cells. Physiological and histological analyses were carried out in Kif5b knockout mice as well as littermate controls. RESULTS: Mice with β-cell specific deletion of Kif5b (Kif5b fl/-: RIP2-Cre) displayed significantly retarded growth as well as slight hyperglycemia in both nonfasting and 16-h fasting conditions compared with control littermates. In addition, Kif5b fl/-: RIP2-Cre mice displayed significant glucose intolerance, which was not due to insulin resistance but was related to an insulin secretory defect in response to glucose challenge. These defects of β-cell function in mutant mice were not coupled with observable changes in islet morphology, islet cell composition, or β-cell size. However, compared with controls, pancreas of Kif5b fl/-: RIP2-Cre mice exhibited both reduced islet size and increased islet number, concomitant with an increased insulin vesicle density in β-cells. CONCLUSIONS: In addition to being essential for maintaining glucose homeostasis and regulating β-cell function, Kif5b may be involved in β-cell development by regulating β-cell proliferation and insulin vesicle synthesis. © 2011 by the American Diabetes Association.
Persistent Identifierhttp://hdl.handle.net/10722/137215
ISSN
2015 Impact Factor: 8.784
2015 SCImago Journal Rankings: 5.185
PubMed Central ID
ISI Accession Number ID
Funding AgencyGrant Number
Hong Kong Research Grants Council (RGC)HKU 7321/04M
HKU 7636/05M
Hong Kong University
RGC GroupHKUST6/CRF/08
Funding Information:

This work was supported by grants from the Hong Kong Research Grants Council (RGC) (HKU 7321/04M, HKU 7636/05M) to J.-D.H., a Hong Kong University Small Project Fund to K.-M.Y., and partial funding by an RGC Group Research Project (HKUST6/CRF/08). No potential conflicts of interest relevant to this article were reported.

References
Grants

 

DC FieldValueLanguage
dc.contributor.authorCui, Jen_HK
dc.contributor.authorWang, Zen_HK
dc.contributor.authorCheng, Qen_HK
dc.contributor.authorLin, Ren_HK
dc.contributor.authorZhang, XMen_HK
dc.contributor.authorLeung, PSen_HK
dc.contributor.authorCopeland, NGen_HK
dc.contributor.authorJenkins, NAen_HK
dc.contributor.authorYao, KMen_HK
dc.contributor.authorHuang, JDen_HK
dc.date.accessioned2011-08-26T14:19:03Z-
dc.date.available2011-08-26T14:19:03Z-
dc.date.issued2011en_HK
dc.identifier.citationDiabetes, 2011, v. 60 n. 1, p. 320-330en_HK
dc.identifier.issn0012-1797en_HK
dc.identifier.urihttp://hdl.handle.net/10722/137215-
dc.description.abstractOBJECTIVE: Suppression of Kinesin-1 by antisense oligonucleotides, or overexpression of dominant-negative acting kinesin heavy chain, has been reported to affect the sustained phase of glucose-stimulated insulin secretion in β-cells in vitro. In this study, we examined the in vivo physiological role of Kinesin-1 in β-cell development and function. RESEARCH DESIGN AND METHODS: A Cre-LoxP strategy was used to generate conditional knockout mice in which the Kif5b gene is specifically inactivated in pancreatic β-cells. Physiological and histological analyses were carried out in Kif5b knockout mice as well as littermate controls. RESULTS: Mice with β-cell specific deletion of Kif5b (Kif5b fl/-: RIP2-Cre) displayed significantly retarded growth as well as slight hyperglycemia in both nonfasting and 16-h fasting conditions compared with control littermates. In addition, Kif5b fl/-: RIP2-Cre mice displayed significant glucose intolerance, which was not due to insulin resistance but was related to an insulin secretory defect in response to glucose challenge. These defects of β-cell function in mutant mice were not coupled with observable changes in islet morphology, islet cell composition, or β-cell size. However, compared with controls, pancreas of Kif5b fl/-: RIP2-Cre mice exhibited both reduced islet size and increased islet number, concomitant with an increased insulin vesicle density in β-cells. CONCLUSIONS: In addition to being essential for maintaining glucose homeostasis and regulating β-cell function, Kif5b may be involved in β-cell development by regulating β-cell proliferation and insulin vesicle synthesis. © 2011 by the American Diabetes Association.en_HK
dc.languageengen_US
dc.publisherAmerican Diabetes Association. The Journal's web site is located at http://diabetes.diabetesjournals.org/en_HK
dc.relation.ispartofDiabetesen_HK
dc.subject.meshAmino Acid Sequence-
dc.subject.meshBlotting, Western-
dc.subject.meshInsulin - deficiency - secretion-
dc.subject.meshInsulin-Secreting Cells - drug effects - physiology-
dc.subject.meshKinesin - antagonists and inhibitors - chemistry - deficiency - drug effects - genetics-
dc.titleTargeted inactivation of Kinesin-1 in pancreatic β-cells in vivo leads to insulin secretory deficiencyen_HK
dc.typeArticleen_HK
dc.identifier.openurlhttp://library.hku.hk:4550/resserv?sid=HKU:IR&issn=0012-1797&volume=60&issue=1&spage=320&epage=330&date=2011&atitle=Targeted+inactivation+of+kinesin-1+in+pancreatic+β-cells+in+vivo+leads+to+insulin+secretory+deficiency-
dc.identifier.emailYao, KM:kmyao@hku.hken_HK
dc.identifier.emailHuang, JD:jdhuang@hkucc.hku.hken_HK
dc.identifier.authorityYao, KM=rp00344en_HK
dc.identifier.authorityHuang, JD=rp00451en_HK
dc.description.naturepublished_or_final_versionen_US
dc.identifier.doi10.2337/db09-1078en_HK
dc.identifier.pmid20870970-
dc.identifier.pmcidPMC3012189-
dc.identifier.scopuseid_2-s2.0-78751513648en_HK
dc.identifier.hkuros191688en_US
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-78751513648&selection=ref&src=s&origin=recordpageen_HK
dc.identifier.volume60en_HK
dc.identifier.issue1en_HK
dc.identifier.spage320en_HK
dc.identifier.epage330en_HK
dc.identifier.eissn1939-327X-
dc.identifier.isiWOS:000286017300039-
dc.publisher.placeUnited Statesen_HK
dc.relation.projectRole of kinesin-mediated intracellular transportation in Alzheimer's Disease-
dc.relation.projectProtein Trafficking: Mechanism and Diseases-
dc.relation.projectFunctions of the ubiquitously expressed kinesin in Purkinje neurons-
dc.identifier.scopusauthoridCui, J=37040458000en_HK
dc.identifier.scopusauthoridWang, Z=37040881000en_HK
dc.identifier.scopusauthoridCheng, Q=25824689200en_HK
dc.identifier.scopusauthoridLin, R=24391138500en_HK
dc.identifier.scopusauthoridZhang, XM=37040847100en_HK
dc.identifier.scopusauthoridLeung, PS=7401748938en_HK
dc.identifier.scopusauthoridCopeland, NG=35374759300en_HK
dc.identifier.scopusauthoridJenkins, NA=35379887700en_HK
dc.identifier.scopusauthoridYao, KM=7403234578en_HK
dc.identifier.scopusauthoridHuang, JD=8108660600en_HK

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