GABAergic System in b-Cells: From Autoimmunity Target to Regeneration Tool

The g-aminobutyric acid (GABA) is a product ofdecarboxylation of the amino acid glutamatemediated by the synthesizing enzyme glutamicacid decarboxylase (GAD) (1–3). Although GABA is a major inhibitory neurotransmitter of the brain, it is produced at high levels in pancreatic islets (4). b-Cells store GABA in synaptic-like microvesicles, and upon its secre-tion, GABA exerts many paracrine functions in pancreatic islets (4). While the total function of GABA in b-cells is incompletely understood (4), its synthesizing enzyme GAD is possibly one of the most significant pancreatic islet b-cell autoantigens (5). GAD is a primary target of autoantibodies, and anti-GAD antibodies are associated with the develop-ment of type 1 diabetes (T1D) (5). GABA AND b-CELLS GABA activates three types of membrane receptors: GABAA and GABAC, which are ligand-gated Cl 2 channels