Understanding and Modulating the Toll Like Receptors (TLRs) and NOD Like Receptors (NLRs) Cross Talk in Type 2 Diabetes
Understanding and Modulating the Toll Like Receptors (TLRs) and NOD Like Receptors (NLRs) Cross Talk in Type 2 Diabetes
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DOI：
10.2174/1573399810666140515112609
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发表时间：
2014-01-01
影响因子：
3.3
通讯作者：
Seshadri, Sriram
中科院分区：
文献类型：
--
作者：
Prajapati, Bhumika;Jena, Prasant Kumar;Seshadri, Sriram
肥胖症和2型糖尿病是主要的健康问题，其特征在于低度炎症，伴随炎症细胞因子的增加，沿着肠道微生物群的变化。Toll样受体（TLR）和NOD样受体（NLR）是非常重要的病原体识别受体，在先天免疫系统中起重要作用。TLR和NLR途径都是通过不同的衔接蛋白介导的;通常发现激活NF-kB，从而诱导促炎细胞因子的表达。已经表明TLR和NLR在炎症介导的胰岛素抵抗的发病机制中具有重要作用，其进一步发展代谢并发症。TLR介导的胰岛素抵抗机制涉及通过TLR配体的活化，例如来自脂肪细胞以及骨骼肌的增加的游离脂肪酸和脂质衍生物。此外，2型糖尿病中肠道微生物群的改变也通过增加血浆LPS水平发挥关键作用，其特异性激活TLR 4并引发炎症介导的胰岛素抵抗。NOD 1和NOD 2可能通过识别肠道微生物群参与糖尿病的发病机制。抗生素对肠道微生物群的调节可能通过TLR和NLR介导的信号传导反应在增加胰岛素敏感性方面起着至关重要的作用，这表明了肥胖、胰岛素抵抗和2型糖尿病的未来治疗方法。本文就TLRs和NLRs在代谢性疾病中的相互作用及其在炎症性疾病发病机制中的相互影响作一综述。
Obesity and Type 2 diabetes are leading health problems which are characterized by low-grade inflammation with an increase in inflammatory cytokines along with the change in the gut microbiota population. Toll like Receptors (TLRs) and NOD like Receptors (NLRs) are very prominent pathogen recognition receptors, which play a significant role in the innate immune system. Both TLRs and NLRs pathways are mediated through different adaptor proteins; commonly found to activate the NF-kB, which induces the expression of proinflammatory cytokines. It has been suggested that TLRs and NLRs have a significant role in the pathogenesis of inflammation mediated insulin resistance, which further develops metabolic complications. TLRs mediated mechanism for insulin resistance involves activation through TLR ligands such as increased free fatty acids and lipid derivatives from adipocytes as well as the skeletal muscles. Moreover, gut microbiota alteration in the type 2 diabetes also plays a key role by increasing the plasma LPS levels, which specifically activates TLR4 and provokes the inflammation mediated insulin resistance. NOD1 and NOD2 are involved in the pathogenesis of diabetes, possibly through the recognition of the gut microbiota. Gut microbiota modulation by antibiotics plays a crucial role in increasing insulin sensitivity, possibly through the TLRs and NLRs mediated signaling responses, which suggest future therapeutic approaches for obesity, insulin resistance and type 2 diabetes. In this review, we focused on the interdependent role of TLRs and NLRs in metabolic diseases and their cross talk for the pathogenesis of inflammatory diseases.