Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/10575
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dc.contributor.authorKebede, Melkamen
dc.contributor.authorFavaloro, Jenny Men
dc.contributor.authorGunton, Jenny Een
dc.contributor.authorLaybutt, D Rossen
dc.contributor.authorShaw, Margareten
dc.contributor.authorWong, Nicoleen
dc.contributor.authorFam, Barbara Cen
dc.contributor.authorAston-Mourney, Kathrynen
dc.contributor.authorRantzau, Christianen
dc.contributor.authorZulli, Anthonyen
dc.contributor.authorProietto, Josephen
dc.contributor.authorAndrikopoulos, Sofianosen
dc.date.accessioned2015-05-16T00:04:42Z
dc.date.available2015-05-16T00:04:42Z
dc.date.issued2008-03-28en
dc.identifier.citationDiabetes 2008; 57(7): 1887-95en
dc.identifier.govdoc18375435en
dc.identifier.otherPUBMEDen
dc.identifier.urihttp://ahro.austin.org.au/austinjspui/handle/1/10575en
dc.description.abstractFructose-1,6-bisphosphatase (FBPase) is a gluconeogenic enzyme that is upregulated in islets or pancreatic beta-cell lines exposed to high fat. However, whether specific beta-cell upregulation of FBPase can impair insulin secretory function is not known. The objective of this study therefore is to determine whether a specific increase in islet beta-cell FBPase can result in reduced glucose-mediated insulin secretion.To test this hypothesis, we have generated three transgenic mouse lines overexpressing the human FBPase (huFBPase) gene specifically in pancreatic islet beta-cells. In addition, to investigate the biochemical mechanism by which elevated FBPase affects insulin secretion, we made two pancreatic beta-cell lines (MIN6) stably overexpressing huFBPase.FBPase transgenic mice showed reduced insulin secretion in response to an intravenous glucose bolus. Compared with the untransfected parental MIN6, FBPase-overexpressing cells showed a decreased cell proliferation rate and significantly depressed glucose-induced insulin secretion. These defects were associated with a decrease in the rate of glucose utilization, resulting in reduced cellular ATP levels.Taken together, these results suggest that upregulation of FBPase in pancreatic islet beta-cells, as occurs in states of lipid oversupply and type 2 diabetes, contributes to insulin secretory dysfunction.en
dc.language.isoenen
dc.subject.otherAnimalsen
dc.subject.otherDiabetes Mellitus, Type 2.enzymology.physiopathologyen
dc.subject.otherEnhancer Elements, Geneticen
dc.subject.otherFatty Acids.pharmacologyen
dc.subject.otherFructose-Bisphosphatase.genetics.metabolismen
dc.subject.otherGene Expression Regulation, Enzymologicen
dc.subject.otherHumansen
dc.subject.otherInsulin.genetics.secretionen
dc.subject.otherInsulin Resistanceen
dc.subject.otherInsulin-Secreting Cells.enzymology.secretionen
dc.subject.otherMiceen
dc.subject.otherMice, Transgenicen
dc.subject.otherPolymerase Chain Reactionen
dc.subject.otherPromoter Regions, Geneticen
dc.subject.otherRatsen
dc.subject.otherTissue Donorsen
dc.titleFructose-1,6-bisphosphatase overexpression in pancreatic beta-cells results in reduced insulin secretion: a new mechanism for fat-induced impairment of beta-cell function.en
dc.typeJournal Articleen
dc.identifier.journaltitleDiabetesen
dc.identifier.affiliationDepartment of Medicine, Heidelberg Repatriation Hospital, University of Melbourne, Heidelberg Heights, Victoria, Australiaen
dc.identifier.doi10.2337/db07-1326en
dc.description.pages1887-95en
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pubmed/18375435en
Appears in Collections:Journal articles

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