• Nepton Soltani, Hongmin Qiu, Mila Aleksic, Yelena Glinka, Fang Zhao, Rui Liu, Yiming Li, Nina Zhang, Rabindranath Chakrabarti, Tiffany Ng, Tianru Jin, Haibo Zhang, Wei-Yang Lu, Zhong-Ping Feng, Gerald J Prud'homme, and Qinghua Wang.
• Division of Endocrinology and Metabolism, the Keenan Research Centre in the Li Ka Shing Knowledge Institute, St. Michael's Hospital, Toronto, ON, Canada M5B 1W8.
• Proc. Natl. Acad. Sci. U.S.A. 2011 Jul 12; 108 (28): 11692-7.

AbstractType 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 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 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.

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