Journal article

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

Melkam Kebede, Jenny Favaloro, Jenny E Gunton, D Ross Laybutt, Margaret Shaw, Nicole Wong, Barbara C Fam, Kathryn Aston-Mourney, Christian Rantzau, Anthony Zulli, Joseph Proietto, Sofianos Andrikopoulos



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 FB..

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