ESPE Abstracts (2018) 89 NA2.2

Induction of Pancreatic Beta-Cell Neogenesis

Patrick Collombat

INSERM, Nice, France

Background: The recent discovery that genetically-modified pancreatic alpha-cells can regenerate and convert into beta-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.

Results: We recently identified GABA as an inducer of alpha-to-beta-like cell conversion in vivo. This conversion induces alpha-cell replacement mechanisms through the mobilization of duct-lining precursor cells that adopt an alpha-cell identity prior to being converted into beta-like cells, solely upon sustained GABA exposure. Importantly, these neo-generated beta-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 alpha-cells and a concomitant increase in beta-like cell counts, suggestive of alpha-to-beta-like cell conversion processes also in humans. The latest advances will be discussed

Conclusions: This newly discovered GABA-induced alpha-cell-mediated beta-like cell neogenesis could therefore represent an unprecedented hope towards improved therapies for diabetes.

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