Rapamycin/GABA combination treatment ameliorates diabetes in NOD mice
Rapamycin/GABA combination treatment ameliorates diabetes in NOD mice
复制标题
雷帕霉素/GABA 联合治疗可改善 NOD 小鼠的糖尿病。
DOI：
10.1016/j.molimm.2016.01.008
复制
发表时间：
2016-05-01
影响因子：
3.6
通讯作者：
Chen, Quan
中科院分区：
文献类型：
--
作者：
He, Sirong;Zhang, Yi;Chen, Quan
1型糖尿病（TiD）是最常见的自身免疫性疾病之一，影响全球近2000万人。T1 D的发病机制的特征在于自身反应性T细胞对产生胰岛素的胰腺β细胞的进行性破坏。免疫调节在新诊断的TlD中保留残余的产生胰岛素的β细胞中的显著作用尚未得到证实。然而，通过不同机制起作用的治疗组合被广泛认为是这方面最有前途的未来治疗方法。单独给予雷帕霉素和γ-氨基丁酸（GABA）对晚期疾病没有影响。相比之下，雷帕霉素/GABA联合治疗有效地抑制了对胰岛细胞的自身免疫反应，改善了近期发病的糖尿病患者的胰岛功能。特别地，在高血糖症发作后，与单独用雷帕霉素或GABA治疗的那些相比，用雷帕霉素/GABA组合治疗的那些显示出糖尿病改善的显著改善。雷帕霉素/GABA联合治疗对非肥胖糖尿病（NOD）小鼠的保护作用通过两种不同的机制发挥。雷帕霉素诱导调节性T细胞，从而抑制针对胰岛细胞的自身免疫反应，这可能与雷帕霉素治疗的NOD小鼠中观察到的胰岛炎减少有关。相比之下，GABA治疗改善了糖尿病NOD小鼠的胰岛功能。我们相信，我们的观察结果是高度相关的建立临床策略，预防和治疗T1 D的未来。(c)2016爱思唯尔有限公司版权所有。
Type 1 diabetes (Ti D) is one of the most common autoimmune diseases, affecting nearly 20 million people worldwide. The pathogenesis of T1D is characterized by the progressive destruction of insulin-producing pancreatic beta-cells by autoreactive T cells. The significant role of immunomodulation in preserving residual insulin-producing beta-cells in newly diagnosed Tl D has not been confirmed yet. However, a combination of treatments acting via distinct mechanisms is widely considered to be the most promising future therapeutic approach in this respect. Rapamycin and gamma-aminobutyric acid (GABA) administration alone showed no effects on late-stage disease. By contrast, combined rapamycin/GABA treatment effectively suppressed autoimmune responses to islet cells and improved islet function in recent-onset diabetes. In particular, after the onset of hyperglycemia, those treated with the rapamycin/GABA combination showed significant amelioration of diabetes amelioration compared to those treated with either rapamycin or GABA alone. This protective effect of the rapamycin/GABA combination treatment in nonobese diabetic (NOD) mice was exerted through two distinct mechanisms. Rapamycin induced regulatory T cells and consequently suppressed targeted autoimmune responses to islet cells, which may be relevant to the reduced insulitis observed in rapamycin-treated NOD mice. By contrast, treatment with GABA improved islet function in diabetic NOD mice. We believe that our observations are highly relevant to establishing clinical strategies for the prevention and treatment of T1D in future. (c) 2016 Elsevier Ltd. All rights reserved.