{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["57(7)"],"submitter":["Kebede M"],"pubmed_abstract":["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."],"journal":["Diabetes"],"pagination":["1887-95"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC2453625"],"repository":["biostudies-literature"],"pubmed_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."],"pmcid":["PMC2453625"],"pubmed_authors":["Aston-Mourney K","Proietto J","Shaw M","Fam BC","Zulli A","Andrikopoulos S","Favaloro J","Gunton JE","Wong N","Laybutt DR","Kebede M","Rantzau C"],"additional_accession":[]},"is_claimable":false,"name":"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.","description":"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.","dates":{"release":"2008-01-01T00:00:00Z","publication":"2008 Jul","modification":"2021-02-20T04:39:09Z","creation":"2019-03-27T00:15:47Z"},"accession":"S-EPMC2453625","cross_references":{"pubmed":["18375435"],"doi":["10.2337/db07-1326"]}}