Edited* by Roger H. Unger, Touchstone Center for Diabetes Research, Dallas, TX, and approved June 2, 2011 (received for review February 23, 2011)
Type 1 diabetes (T1D) is an autoimmune disease characterized by insulitis and islet β-cell loss. Thus, an effective therapy may require β-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 β-cells and immune system. Unlike in adult brain or islet α-cells in which GABA exerts hyperpolarizing effects, in islet β-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 β-cell mass and prevents the development of T1D. Remarkably, in severely diabetic mice, GABA restores β-cell mass and reverses the disease. Furthermore, GABA suppresses insulitis and systemic inflammatory cytokine production. The β-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.
↵1Present address: Department of Physiology, Faculty of Medicine, Hormozgan University of Medical Science, Bandar-Abbas, 7919693116 Iran.
↵2N.S. and H.Q. contributed equally to this work.
↵3Present address: First Teaching Hospital of Xinjiang Medical University, Urumqi 830054, China.
Author contributions: N.S., G.J.P., and Q.W. designed research; N.S., H.Q., M.A., Y.G., F.Z., R.L., N.Z., R.C., T.N., H.Z., Z.-P.F., and Q.W. performed research; N.S., H.Q., M.A., Y.G., F.Z., R.L., Y.L., N.Z., R.C., T.N., T.J., H.Z., W.-Y.L., Z.-P.F., G.J.P., and Q.W. analyzed data; and N.S., G.J.P., and Q.W. wrote the paper.
Conflict of interest statement: A patent application authored by N.S and Q.W. has been submitted for an invention related to this study.
↵*This Direct Submission article had a prearranged editor.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1102715108/-/DCSupplemental.
