التفاصيل البيبلوغرافية
| العنوان: |
COUP-TFII Controls Mouse Pancreatic β-Cell Mass through GLP-1-β-Catenin Signaling Pathways. |
| المؤلفون: |
Boutant, Marie, Ramos, Oscar Henrique Pereira, Tourrel-Cuzin, Cécile, Movassat, Jamileh, Ilias, Anissa, Vallois, David, Planchais, Julien, Pégorier, Jean-Paul, Schuit, Frans, Petit, Patrice X., Bossard, Pascale, Maedler, Kathrin, Grapin-Botton, Anne, Vasseur-Cognet, Mireille |
| المصدر: |
PLoS ONE; Jan2012, Vol. 7 Issue 1, p1-15, 15p |
| مصطلحات موضوعية: |
CATENINS, TRANSCRIPTION factors, OVALBUMINS, INSULIN, BLOOD sugar, MICE, APOPTOSIS |
| مستخلص: |
Background: The control of the functional pancreatic β-cell mass serves the key homeostatic function of releasing the right amount of insulin to keep blood sugar in the normal range. It is not fully understood though how β-cell mass is determined. Methodology/Principal Findings: Conditional chicken ovalbumin upstream promoter transcription factor II (COUP-TFII)- deficient mice were generated and crossed with mice expressing Cre under the control of pancreatic duodenal homeobox 1 (pdx1) gene promoter. Ablation of COUP-TFII in pancreas resulted in glucose intolerance. Beta-cell number was reduced at 1 day and 3 weeks postnatal. Together with a reduced number of insulin-containing cells in the ductal epithelium and normal β-cell proliferation and apoptosis, this suggests decreased β-cell differentiation in the neonatal period. By testing islets isolated from these mice and cultured β-cells with loss and gain of COUP-TFII function, we found that COUP-TFII induces the expression of the β-catenin gene and its target genes such as cyclin D1 and axin 2. Moreover, induction of these genes by glucagon-like peptide 1 (GLP-1) via β-catenin was impaired in absence of COUP-TFII. The expression of two other target genes of GLP-1 signaling, GLP-1R and PDX-1 was significantly lower in mutant islets compared to control islets, possibly contributing to reduced β-cell mass. Finally, we demonstrated that COUP-TFII expression was activated by the Wnt signaling-associated transcription factor TCF7L2 (T-cell factor 7-like 2) in human islets and rat β-cells providing a feedback loop. Conclusions/Significance: Our findings show that COUP-TFII is a novel component of the GLP-1 signaling cascade that increases β-cell number during the neonatal period. COUP-TFII is required for GLP-1 activation of the β-catenin-dependent pathway and its expression is under the control of TCF7L2. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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