Gimmicks of gamma-aminobutyric acid (GABA) in pancreatic β-cell regeneration through transdifferentiation of pancreatic α- to β-cells.

In vivo regeneration of lost or dysfunctional islet β cells can fulfill the promise of improved therapy for diabetic patients. To achieve this, many mitogenic factors have been attempted, including gamma-aminobutyric acid (GABA). GABA remarkably affects pancreatic islet cells' (α cells and β cells) function through paracrine and/or autocrine binding to its membrane receptors on these cells. GABA has also been studied for promoting the transformation of α cells to β cells. Nonetheless, the gimmickry of GABA-induced α-cell transformation to β cells has two different perspectives. On the one hand, GABA was found to induce α-cell transformation to β cells in vivo and insulin-secreting β-like cells in vitro. On the other hand, GABA treatment showed that it has no α- to β-cell transformation response. Here, we will summarize the physiological effects of GABA on pancreatic islet β cells with an emphasis on its regenerative effects for transdifferentiation of islet α cells to β cells. We will also critically discuss the controversial results about GABA-mediated transdifferentiation of α cells to β cells.