Department of Cell and Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran.
Inflammopharmacology. 2018 Jun;26(3):685-698. doi: 10.1007/s10787-018-0458-0. Epub 2018 Mar 5.
Interleukin 6 (IL-6), a multifunctional cytokine, has been implicated in the pathophysiology of type 2 diabetes (T2D). The elevated circulating level of IL-6 is an independent predictor of T2D and is considered to be involved in the development of inflammation, insulin resistance and β-cell dysfunction. On the other hand, an increasing number of evidence suggests that IL-6 has an anti-inflammatory role and improves glucose metabolism. The complex signal transduction mechanism of IL-6 may help explain the pleiotropic nature of the cytokine. IL-6 acts via two distinct signalling pathways called classic signalling and trans-signalling. While both signalling modes lead to activation of the same receptor subunit, their final biological effects are completely different. The aim of this review is to summarize our current knowledge about the role of IL-6 in the development of T2D. We will also discuss the importance of specific blockade of IL-6 trans-signalling rather than inhibiting both signalling pathways as a therapeutic strategy for the treatment of T2D and its associated macrovascular complications.
白细胞介素 6（IL-6）是一种多功能细胞因子，与 2 型糖尿病（T2D）的病理生理学有关。循环中升高的 IL-6 水平是 T2D 的独立预测因子，被认为参与炎症、胰岛素抵抗和β细胞功能障碍的发生。另一方面，越来越多的证据表明，IL-6 具有抗炎作用并改善葡萄糖代谢。IL-6 的复杂信号转导机制可能有助于解释细胞因子的多效性。IL-6 通过两种不同的信号通路发挥作用，称为经典信号通路和转信号通路。虽然这两种信号模式都导致相同的受体亚基激活，但它们的最终生物学效应完全不同。本综述的目的是总结我们目前对 IL-6 在 T2D 发展中的作用的认识。我们还将讨论特异性阻断 IL-6 转信号通路而不是抑制两种信号通路作为治疗 T2D 及其相关大血管并发症的治疗策略的重要性。
