GABA exerts protective and regenerative effects on islet beta cells and reverses diabetes

Type 1 diabetes (T1D) is an autoimmune disease characterized by insulitis and islet beta-cell loss. Thus, an effective therapy may require beta-cell restoration and immune suppression. Currently, there is no treatment that can achieve both goals efficiently. We report here that GABA exerts antidiabetic effects by acting on both the islet beta-cells and immune system. Unlike in adult brain or islet alpha-cells in which GABA exerts hyperpolarizing effects, in islet beta-cells, GABA produces membrane depolarization and Ca2+ influx, leading to the activation of PI3-K/Akt-dependent growth and survival pathways. This provides a potential mechanism underlying our in vivo findings that GABA therapy preserves beta-cell mass and prevents the development of T1D. Remarkably, in severely diabetic mice, GABA restores beta-cell mass and reverses the disease. Furthermore, GABA suppresses insulitis and systemic inflammatory cytokine production. The beta-cell regenerative and immunoinhibitory effects of GABA provide insights into the role of GABA in regulating islet cell function and glucose homeostasis, which may find clinical application.