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. doi: 10.1073/pnas.1102715108. Epub 2011 Jun 27.
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 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.
1 型糖尿病（T1D）是一种自身免疫性疾病，其特征是胰岛炎和胰岛β细胞丧失。因此，有效的治疗方法可能需要β细胞的恢复和免疫抑制。目前，还没有一种治疗方法能够有效地达到这两个目标。我们在这里报告，GABA 通过作用于胰岛β细胞和免疫系统发挥抗糖尿病作用。与在成年大脑或胰岛α细胞中 GABA 产生超极化作用不同，在胰岛β细胞中，GABA 产生膜去极化和 Ca(2+)内流，导致 PI3-K/Akt 依赖性生长和存活途径的激活。这为我们的体内发现提供了一个潜在的机制，即 GABA 治疗可以保护β细胞的质量并预防 T1D 的发展。值得注意的是，在严重糖尿病的小鼠中，GABA 可以恢复β细胞的质量并逆转疾病。此外，GABA 抑制胰岛炎和全身炎症细胞因子的产生。GABA 的β细胞再生和免疫抑制作用为 GABA 在调节胰岛细胞功能和葡萄糖稳态中的作用提供了新的见解，这可能具有临床应用价值。
