Please use this identifier to cite or link to this item:
Full metadata record
DC FieldValueLanguage
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.identifier.citationDiabetes 2008; 57(7): 1887-95en
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.subject.otherDiabetes Mellitus, Type 2.enzymology.physiopathologyen
dc.subject.otherEnhancer Elements, Geneticen
dc.subject.otherFatty Acids.pharmacologyen
dc.subject.otherGene Expression Regulation, Enzymologicen
dc.subject.otherInsulin Resistanceen
dc.subject.otherInsulin-Secreting Cells.enzymology.secretionen
dc.subject.otherMice, Transgenicen
dc.subject.otherPolymerase Chain Reactionen
dc.subject.otherPromoter Regions, Geneticen
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.affiliationDepartment of Medicine, Heidelberg Repatriation Hospital, University of Melbourne, Heidelberg Heights, Victoria, Australiaen
Appears in Collections:Journal articles

Files in This Item:
There are no files associated with this item.

Items in AHRO are protected by copyright, with all rights reserved, unless otherwise indicated.