Please use this identifier to cite or link to this item: http://ahro.austin.org.au/austinjspui/handle/1/10575
Title: Fructose-1,6-bisphosphatase overexpression in pancreatic beta-cells results in reduced insulin secretion: a new mechanism for fat-induced impairment of beta-cell function.
Authors: Kebede, Melkam;Favaloro, Jenny M;Gunton, Jenny E;Laybutt, D Ross;Shaw, Margaret;Wong, Nicole;Fam, Barbara C;Aston-Mourney, Kathryn;Rantzau, Christian;Zulli, Anthony;Proietto, Joseph;Andrikopoulos, Sofianos
Affiliation: Department of Medicine, Heidelberg Repatriation Hospital, University of Melbourne, Heidelberg Heights, Victoria, Australia.
Issue Date: 28-Mar-2008
Citation: Diabetes 2008; 57(7): 1887-95
Abstract: 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.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.
Internal ID Number: 18375435
URI: http://ahro.austin.org.au/austinjspui/handle/1/10575
DOI: 10.2337/db07-1326
URL: http://www.ncbi.nlm.nih.gov/pubmed/18375435
Type: Journal Article
Subjects: Animals
Diabetes Mellitus, Type 2.enzymology.physiopathology
Enhancer Elements, Genetic
Fatty Acids.pharmacology
Fructose-Bisphosphatase.genetics.metabolism
Gene Expression Regulation, Enzymologic
Humans
Insulin.genetics.secretion
Insulin Resistance
Insulin-Secreting Cells.enzymology.secretion
Mice
Mice, Transgenic
Polymerase Chain Reaction
Promoter Regions, Genetic
Rats
Tissue Donors
Appears in Collections:Journal articles

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