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

ABSTRACT

Type 1 diabetes (T1D) is an autoimmune disease characterized by insulitis and islet ß-cell loss. Thus, an effective therapy may require ß-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 ß-cells and immune system. Unlike in adult brain or islet α-cells in which GABA exerts hyperpolarizing effects, in islet ß-cells, GABA produces membrane depolarization and Ca(2+) 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 ß-cell mass and prevents the development of T1D. Remarkably, in severely diabetic mice, GABA restores ß-cell mass and reverses the disease. Furthermore, GABA suppresses insulitis and systemic inflammatory cytokine production. The ß-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.