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http://purl.uniprot.org/citations/18375435http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18375435http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/18375435http://www.w3.org/2000/01/rdf-schema#comment"

Objective

Fructose-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.

Research design and methods

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.

Results

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.

Conclusions

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."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.org/dc/terms/identifier"doi:10.2337/db07-1326"xsd:string
http://purl.uniprot.org/citations/18375435http://purl.org/dc/terms/identifier"doi:10.2337/db07-1326"xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Shaw M."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Shaw M."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Favaloro J."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Favaloro J."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Wong N."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Wong N."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Andrikopoulos S."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Andrikopoulos S."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Aston-Mourney K."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Aston-Mourney K."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Fam B.C."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Fam B.C."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Gunton J.E."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Gunton J.E."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Kebede M."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Kebede M."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Laybutt D.R."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Laybutt D.R."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Proietto J."xsd:string
http://purl.uniprot.org/citations/18375435http://purl.uniprot.org/core/author"Proietto J."xsd:string
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