English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT

Released

Journal Article

The inactivation of Arx in pancreatic alpha-cells triggers their neogenesis and conversion into functional beta-like cells.

MPS-Authors
/persons/resource/persons15488

Mansouri,  A.
Research Group of Molecular Cell Differentiation, MPI for biophysical chemistry, Max Planck Society;

Fulltext (public)

1943482.pdf
(Publisher version), 15MB

Supplementary Material (public)
There is no public supplementary material available
Citation

Courtney, M., Gjernes, E., Druelle, N., Ravaud, C., Vieira, A., Ben-Othman, N., et al. (2013). The inactivation of Arx in pancreatic alpha-cells triggers their neogenesis and conversion into functional beta-like cells. PLoS Genetics, 9(10): e1003934. doi:10.1371/journal.pgen.1003934.


Cite as: http://hdl.handle.net/11858/00-001M-0000-0015-8811-C
Abstract
Recently, it was demonstrated that pancreatic new-born glucagon-producing cells can regenerate and convert into insulinproducing beta-like cells through the ectopic expression of a single gene, Pax4. Here, combining conditional loss-of-function and lineage tracing approaches, we show that the selective inhibition of the Arx gene in alpha-cells is sufficient to promote the conversion of adult alpha-cells into beta-like cells at any age. Interestingly, this conversion induces the continuous mobilization of duct-lining precursor cells to adopt an endocrine cell fate, the glucagon(+) cells thereby generated being subsequently converted into beta-like cells upon Arx inhibition. Of interest, through the generation and analysis of Arx and Pax4 conditional double-mutants, we provide evidence that Pax4 is dispensable for these regeneration processes, indicating that Arx represents the main trigger of alpha-cell-mediated beta-like cell neogenesis. Importantly, the loss of Arx in alpha-cells is sufficient to regenerate a functional beta-cell mass and thereby reverse diabetes following toxin-induced beta-cell depletion. Our data therefore suggest that strategies aiming at inhibiting the expression of Arx, or its molecular targets/co-factors, may pave new avenues for the treatment of diabetes.