GABA-mediated alpha-to-beta-like cell neogenesis – GABANEO

Over the past few decades, diabetes has become one of the most widespread metabolic disorders with epidemic dimensions affecting almost 9% of the world’s population. Despite major efforts and modern treatments, type 1 diabetic patients display a higher risk of cardiovascular complications and an altered quality of life. There is therefore a need for alternative therapies. Towards this aim, using the mouse as a model, we recently demonstrated that long-term GABA (Gamma-AminoButyric Acid) treatment can induce a continuous (but controllable) regeneration of pancreatic a-cells and their subsequent conversion into ß-like cells, the latter being capable of reversing several times the consequences of chemically-induced diabetes in vivo. Importantly, GABA can also convert human a-cells into ß-like cells.

We therefore propose to test GABA activities in Type 1 diabetic patients (through a pilot clinical trial - NovoNordisk). Concomitant analyses, using the mouse as a model, will allow us to gain further insights into its mechanisms of action and to determine whether one could further improve ß-like cell neogenesis by potentiating GABA activities and/or protecting regenerated cells. Furthermore, we will also verify whether alternative pancreatic cell subtypes could represent untapped sources for ß-cell regeneration.