Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2012) 29 P1225

ICEECE2012 Poster Presentations Obesity (114 abstracts)

Effect of secreted frizzled-related protein 2 (sFRP2) from adipose tissue on pancreatic cell function

I. Bujalska , E. Rabbitt , L. Gathercole & P. Stewart


University of Birmingham, Birmingham, UK.


The detrimental effect of excessive obesity on insulin resistance is well established. The expansion of adipose tissue is dependent on two processes: adipogenesis and angiogenesis and the Wnt signalling pathway has been reported to affect both. In adipose tissue the Wnt signalling pathway functions in a converse manner: increasing commitment of mesenchymal stem cells to preadipocytes and inhibiting differentiation of preadipocytes to mature adipocytes by decreasing expression of CEBPα and PPARγ.

One of the antagonists of the canonical Wnt signalling pathway is secreted frizzled-related protein 2 (sFRP2) however, recent studies have identified sFRP2 as a novel factor stimulating angiogenesis via a non-canonical, calcineurin/NFAT signalling pathway.

Expression of sFRP2 and Wnt receptors, Fzd1 and Fzd2, mRNA has been reported in preadipocytes and Wnt signalling is also known to be involved in pancreatic islet function, insulin production and secretion. We hypothesised that sFRP2 secreted from adipose tissue could provide a link between obesity and diabetes through a deleterious action on beta cells/ insulin secretion.

Human omental (OM) and subcutaneous (SC) adipose tissues expressed high levels of sFRP2 mRNA with more in OM than SC adipocytes (3.6-fold increase, n=8, p=0.003). In mouse, sFRP2 mRNA was present in gonadal and subcutaneous fats but absent in liver, pancreas and pancreatic α- and β-cell lines. All mouse tissues and cells studied were positive for Wnt signalling receptors Fzd1 and Fzd2. Proliferating mouse pancreatic α- and β-cells treated with recombinant mouse sFRP2 protein (10 ng to 200 ng/ml) for 4 days, showed a dose-dependent decrease in proliferation rates in β-cells (10 ng/ml: 96%, 100 ng/ml: 84%, 200 ng/ml: 72 vs 100% control, P<0.01) but not α-cells or the human preadipocyte cell line, ChubS7.

We postulate that secreted sFRP2 from expanding adipose tissue could have a harmful effect on pancreatic beta cell function and contribute to the pathogenesis of insulin resistance in human obesity.

Declaration of interest: The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research project.

Funding: This research did not receive any specific grant from any funding agency in the public, commercial or not-for-profit sector.

Volume 29

15th International & 14th European Congress of Endocrinology

European Society of Endocrinology 

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