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- Title
Identification and Characterization of a Mouse Islet Cell Subpopulation Expressing High Levels of the Transcription Factor Pax4.
- Authors
Brun, Thierry; Herrera, Pedro; Brighhouse, Dale; Wollheim, Claes B.; Gauthier, Benoit R.
- Abstract
We previously demonstrated that Pax4 is implicated in rat and human islet beta-cell proliferation and survival by inducing the c-myc-Id2 pathway as well as the anti-apoptotic gene bcl-xl. To further investigate the critical function of Pax4 in islet mass adaptation in response to physiological stimuli in vivo, we took advantage of a transgenic mouse model expressing the EGFP cDNA under the transcriptional control of the pax4 gene promoter. Intriguingly, we found that a fraction of islet cells derived from these mice exhibited high levels of EGFP suggesting the existence of distinct Pax4 expressing beta-cell subpopulations. The aim of the current study was therefore to establish the phenotypic profile of these putative Pax4-enriched beta-cells. To achieve this goal, freshly isolated islet cells were dispersed by trypsin digestion and FACS purified according to cell size and EGFP fluorescence. 22% of beta-coils were found to exhibit higher EGFP fluorescence as compared to normal beta-cells. Consistent with the latter, immunofluorescence studies revealed that 24% of islet cells were EGFP-, insulin- and GLUT2-positive whereas 4% were EGFP-positive but insulin- and GLUT2-negative. Quantitative PCR revealed that endogenous levels of Pax4, Id2 and Bcl-xL transcripts were increased by 7.1-, 2.0-, 2.3- fold, respectively, in the EGFP-positive population as compared to EGFP-negative cells while Pdx-1 mRNA levels were unaltered in both populations. Interestingly, the two beta-cell subpopulations responded similarly to glucose-induced and forskolin/IBMX-induced insulin secretion and contained similar hormone protein levels. Activin A, betacellulin and GLP-1 treatment resulted in a 2-fold increase in Pax4 mRNA levels specifically in EGFP-positive beta-cells. These results clearly establish the existence of a bona fide beta-cell subpopulation in mice that expresses higher levels of Pax4 mRNA and which may be prone to mitogen-induced proliferation.
- Subjects
CELL proliferation; ISLANDS of Langerhans; PANCREATIC beta cells; TRANSCRIPTION factors; MESSENGER RNA; INSULIN; LABORATORY mice
- Publication
Diabetes, 2007, Vol 56, pA424
- ISSN
0012-1797
- Publication type
Article