Gimmicks of gamma‐aminobutyric acid in pancreatic β‐cell regeneration through transdifferentiation of pancreatic α cells to β cells

In vivo regeneration of lost or dysfunctional islet beta 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' (alpha cells and beta 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 alpha cells to beta cells. Nonetheless, the gimmickry of GABA-induced alpha-cell transformation to beta cells has two different perspectives. On the one hand, GABA was found to induce alpha-cell transformation to beta cells in vivo and insulin-secreting beta-like cells in vitro. On the other hand, GABA treatment showed that it has no alpha- to beta-cell transformation response. Here, we will summarize the physiological effects of GABA on pancreatic islet beta cells with an emphasis on its regenerative effects for transdifferentiation of islet alpha cells to beta cells. We will also critically discuss the controversial results about GABA-mediated transdifferentiation of alpha cells to beta cells.