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
Data(s) |
01/07/2008
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Resumo |
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.<br /><br />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.<br /><br />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.<br /><br />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. <br /> |
Identificador | |
Idioma(s) |
eng |
Publicador |
American Diabetes Association |
Relação |
http://dro.deakin.edu.au/eserv/DU:30047460/aston-fructoseone-2008.pdf http://dx.doi.org/10.2337/db07-1326 |
Direitos |
2008, by the American Diabetes Association |
Tipo |
Journal Article |