Therapeutic vaccine against DPP4 improves glucose metabolism in mice
Therapeutic vaccine against DPP4 improves glucose metabolism in mice
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DOI：
10.1073/pnas.1322009111
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发表时间：
2014-04-01
影响因子：
11.1
通讯作者：
Rakugi, Hiromi
中科院分区：
文献类型：
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作者：
Pang, Zhengda;Nakagami, Hironori;Rakugi, Hiromi
2型糖尿病患病率的增加与显著的经济负担相关。我们开发了一种二肽基肽酶4（DPP 4）靶向免疫疗法，以提高胰高血糖素样肽1激素水平，改善胰岛素敏感性，用于预防和治疗2型糖尿病。在C57 BL/6 J小鼠中用DPP 4疫苗免疫成功地增加了DPP 4滴度，抑制了血浆DPP 4活性，并诱导了血浆胰高血糖素样肽1水平的增加。此外，这种升高的滴度持续3个月。在喂食高脂饮食的小鼠中，DPP 4疫苗接种导致餐后葡萄糖波动和胰岛素敏感性改善，并且在糖尿病KK-A（y）和db/db小鼠品系中，DPP 4疫苗接种显著降低葡萄糖波动并增加血浆胰岛素和胰腺胰岛素含量。重要的是，用DPP 4本身攻击后T细胞没有被激活，这表明该疫苗不诱导细胞介导的自身免疫。此外，在表达DPP 4的细胞和组织中未检测到显著的免疫介导的损伤。因此，这种DPP 4疫苗可能为糖尿病患者提供一种治疗替代方案。
The increasing prevalence of type 2 diabetes mellitus is associated with a significant economic burden. We developed a dipeptidyl peptidase 4 (DPP4)-targeted immune therapy to increase glucagon-like peptide 1 hormone levels and improve insulin sensitivity for the prevention and treatment of type 2 diabetes mellitus. Immunization with the DPP4 vaccine in C57BL/6J mice successfully increased DPP4 titer, inhibited plasma DPP4 activity, and induced an increase in the plasma glucagon-like peptide 1 level. Moreover, this elevated titer was sustained for 3 mo. In mice fed a high-fat diet, DPP4 vaccination resulted in improved postprandial glucose excursions and insulin sensitivity and, in the diabetic KK-A(y) and db/db mice strains, DPP4 vaccination significantly reduced glucose excursions and increased both plasma insulin and pancreatic insulin content. Importantly, T cells were not activated following challenge with DPP4 itself, which suggests that this vaccine does not induce cell-mediated autoimmunity. Additionally, no significant immune-mediated damage was detected in cells and tissues where DPP4 is expressed. Thus, this DPP4 vaccine may provide a therapeutic alternative for patients with diabetes.