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

Kebede, Melkam, Favaloro, Jenny, Gunton, Jenny E., Laybutt, D. Ross, Shaw, Margaret, Wong, Nicole, Fam, Barbara C., Aston-Mourney, Kathryn, Rantzau, Christian, Zulli, Anthony, Proietto, Joseph and Andrikopoulos, Sofianos 2008, 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, Diabetes, vol. 57, no. 7, pp. 1887-1895.

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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
Formatted title Fructose-1,6-Bisphosphatase overexpression in pancreatic β-cells results in reduced insulin secretion : a new mechanism for fat-induced impairment of β-cell function
Author(s) Kebede, Melkam
Favaloro, Jenny
Gunton, Jenny E.
Laybutt, D. Ross
Shaw, Margaret
Wong, Nicole
Fam, Barbara C.
Aston-Mourney, Kathryn
Rantzau, Christian
Zulli, Anthony
Proietto, Joseph
Andrikopoulos, Sofianos
Journal name Diabetes
Volume number 57
Issue number 7
Start page 1887
End page 1895
Total pages 9
Publisher American Diabetes Association
Place of publication Alexandria, Va
Publication date 2008-07
ISSN 0012-1797
1939-327X
Summary 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.
Language eng
Field of Research 119999 Medical and Health Sciences not elsewhere classified
Socio Economic Objective 970111 Expanding Knowledge in the Medical and Health Sciences
HERDC Research category C1.1 Refereed article in a scholarly journal
Copyright notice ©2008, by the American Diabetes Association
Persistent URL http://hdl.handle.net/10536/DRO/DU:30047460

Document type: Journal Article
Collection: School of Medicine
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