Department of Cell and Molecular Biology, Madras Diabetes Research Foundation and Dr. Mohan's Diabetes Specialities Centre, Gopalapuram, Chennai, India.
Cytokine. 2013 Nov;64(2):564-70. doi: 10.1016/j.cyto.2013.08.003. Epub 2013 Sep 6.
Despite the well known role of nucleotide oligomerization domain (NOD) receptor proteins in innate immunity, their association with diabetes is less explored. Here we report the transcriptional level of NODs and their downstream molecular signatures in CD14(+) monocytes from subjects with different grades of glucose tolerance. NOD1 and NOD2 mRNA expression were significantly up-regulated in monocytes from patients with type 2 diabetes (T2DM) and positively correlated with HOMA-IR and poor glycemic control. Patients with T2DM also exhibited increased monocyte activation markers (CD11b and CD36) and proinflammatory signals downstream of NOD (RIPK2 and NFκB) along with the increased circulatory levels of TNF-α and IL-6. In vitro stimulation of monocytes with NOD specific ligands-i-EDAP and MDP significantly up regulated the mRNA expression of NOD1 and NOD2 respectively in T2DM. Our study exposes up regulation of NODs in monocytes as an important component of inflammation and insulin resistance in patients with T2DM.
尽管核苷酸寡聚化结构域（NOD）受体蛋白在先天免疫中具有众所周知的作用，但它们与糖尿病的关联尚未得到充分探索。在这里，我们报告了不同葡萄糖耐量受试者中 CD14(+)单核细胞中 NOD 及其下游分子特征的转录水平。2 型糖尿病（T2DM）患者的单核细胞中 NOD1 和 NOD2 mRNA 表达明显上调，与 HOMA-IR 和血糖控制不良呈正相关。T2DM 患者还表现出单核细胞活化标志物（CD11b 和 CD36）和 NOD 下游促炎信号（RIPK2 和 NFκB）的增加，以及 TNF-α和 IL-6 的循环水平升高。用 NOD 特异性配体-i-EDAP 和 MDP 体外刺激单核细胞，分别显著上调 T2DM 中 NOD1 和 NOD2 的 mRNA 表达。我们的研究揭示了 NOD 在单核细胞中的上调是 T2DM 患者炎症和胰岛素抵抗的重要组成部分。
