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

Journal Contribution - Journal Article

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.

Journal: Cell (Cambridge)
ISSN: 0092-8674
Issue: 1-2
Volume: 168
Pages: 73-85
Publication year:2017
Keywords:Animals, Basic Helix-Loop-Helix Transcription Factors, Cell Differentiation/drug effects, Diabetes Mellitus/chemically induced, Glucagon-Secreting Cells/cytology, Humans, Insulin-Secreting Cells/cytology, Islets of Langerhans/cytology, Male, Mice, Nerve Tissue Proteins, Rats, Rats, Wistar, gamma-Aminobutyric Acid/administration & dosage
CSS-citation score:4