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Cell. 2017 Jan 12;168(1-2):73-85.e11. doi: 10.1016/j.cell.2016.11.002. Epub 2016 Dec 1.

Long-Term GABA Administration Induces Alpha Cell-Mediated Beta-like Cell Neogenesis.

Author information

1
Université Côte d'Azur, Inserm, CNRS, iBV, 06108 Nice, France.
2
Centre Commun de Microscopie Appliquée, Université de Nice-Sophia Antipolis, 06108 Nice, France.
3
Beta Cell Neogenesis, Vrije Universiteit Brussel, Laarbeeklaan 103, 1090 Brussels, Belgium.
4
ULB Center for Diabetes Research, Medical Faculty, Université Libre de Bruxelles (ULB), 808 Route de Lennik, 1070 Brussels, Belgium.
5
University Lille, Inserm, CHU Lille, U1190 Translational Research for Diabetes, European Genomic Institute for Diabetes, EGID, 59000 Lille, France.
6
Translational Stem Cell Biology, Danish Stem Cell Center (Danstem), University of Copenhagen, DK-2200 Copenhagen, Denmark.
7
Department of Molecular Developmental Biology, Max-Planck Institute for Biophysical Chemistry, Am Fassberg, 37077 Göttingen, Germany; Department of Clinical Neurophysiology, University of Göttingen, Robert-Koch Strasse 40, 37075 Göttingen, Germany.
8
Université Côte d'Azur, Inserm, CNRS, iBV, 06108 Nice, France; Genome and Stem Cell Center, GENKOK, Erciyes University, 38039 Kayseri, Turkey. Electronic address: collombat@unice.fr.

Abstract

The recent discovery that genetically modified α cells can regenerate and convert into β-like cells in vivo holds great promise for diabetes research. However, to eventually translate these findings to human, it is crucial to discover compounds with similar activities. Herein, we report the identification of GABA as an inducer of α-to-β-like cell conversion in vivo. This conversion induces α cell replacement mechanisms through the mobilization of duct-lining precursor cells that adopt an α cell identity prior to being converted into β-like cells, solely upon sustained GABA exposure. Importantly, these neo-generated β-like cells are functional and can repeatedly reverse chemically induced diabetes in vivo. Similarly, the treatment of transplanted human islets with GABA results in a loss of α cells and a concomitant increase in β-like cell counts, suggestive of α-to-β-like cell conversion processes also in humans. This newly discovered GABA-induced α cell-mediated β-like cell neogenesis could therefore represent an unprecedented hope toward improved therapies for diabetes.

KEYWORDS:

Arx; GABA; Pax4; diabetes; endocrine pancreas; mouse; β cell regeneration

PMID:
27916274
DOI:
10.1016/j.cell.2016.11.002
[Indexed for MEDLINE]
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