摘要
胰岛素由胰岛β细胞分泌,经胰岛素信号通路发挥作用。当机体肥胖或其他原因导致胰岛素信号通路受阻时,引起体内胰岛素抵抗(insulin resistance,IR),胰岛素抵抗与低度炎症关系密切。促炎因子,例如肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1β,IL-1β)、白细胞介素-6(interleukin-6,IL-6)等可抑制胰岛素受体底物(insulin receptor substrate,IRS)酪氨酸磷酸化,发生丝氨酸磷酸化,导致胰岛素受体细胞或靶器官对葡萄糖的摄取和利用下降。Toll样受体2(Toll-like receptor 2,TLR2)是一种重要的模式识别受体,可与TLR1或TLR6结合形成二聚体,与炎症和胰岛素信号通路关系密切,TLR2通过髓系分化因子88(myeloid differentiation factor 88,MyD88)依赖途径激活核因子-κB(nuclear factor,NF-κB)和激活蛋白1(activator protein 1,AP-1),上调促炎基因的转录。巨噬细胞是天然免疫系统中重要一员,可参于体内促炎因子和抗炎因子的调节。TLR2于巨噬细胞表面表达。在脂肪酸(fatty acids)的诱导下,TLR2通过上调促炎基因使巨噬细胞向M1表型极化,M1表型巨噬细胞分泌促炎因子,下调胰岛素靶器官对胰岛素的敏感性。本文拟对TLR2基因和巨噬细胞极化对胰岛素抵抗的影响,以及三者的相关性做一简要综述,从分子水平探讨胰岛素抵抗的发生机制,为胰岛素抵抗的相关研究提供理论参考。
Insulin is secreted by isletβcells and functions through the insulin signaling pathway.When the insulin signaling pathway is blocked due to obesity or some reasons,insulin resistance(IR)is induced in vivo,which is closely related to low-grade inflammation.Proinflammatory factors such as tumor necrosis factor-α(TNF-α),interleukin-1β(IL-1β)or interleukin-6(IL-6),inhibit tyrosine phosphorylation of insulin receptor substrate,and serine phosphorylation occurs,resulting in decreased glucose uptake and utilization by insulin receptor cells or target organs.Toll-like receptor 2(TLR2)is an important pattern recognition receptor.TLR2 can form a dimer with TLR1 or TLR6,which is closely related to inflammation and the insulin signaling pathway.TLR2 activates nuclear factor-κB(NF-κB)and activator protein 1(AP-1)through the myeloid differentiation factor 8(MyD88)-dependent pathway to up-regulate the transcription of proinflammatory genes.Macrophage is an important member of the natural immune system,which is involved in the regulation of proinflammatory factors and anti-inflammatory factors.TLR2 is expressed on the surface of macrophages.Under the induction of fatty acids,TLR2 polarizes macrophages to the M1 phenotype by up-regulating pro-inflammatory genes.M1-like macrophages secrete proinflammatory factors and affect the role of insulin.In this paper,we review the effects of the TLR2 gene and macrophage polarization on insulin resistance as well as the correlation among them.The mechanism of insulin resistance is discussed at the molecular level,which provides a theoretical reference for the research of insulin resistance.
作者
马玉
郭豪
常晓彤
MA Yu;GUO Hao;CHANG Xiao-Tong(Key Laboratory of Clinical Diagnostics,Hebei North University,Zhangjiakou 075000,Hebei,China)
出处
《中国生物化学与分子生物学报》
CAS
CSCD
北大核心
2020年第5期527-532,共6页
Chinese Journal of Biochemistry and Molecular Biology
基金
河北省高等学校科学技术研究重点项目(No.ZD2018076)
河北省研究生创新资助项目(No.CXZZSS2019145)
河北省高等学校科学技术研究项目(No.Z018032)资助。
关键词
胰岛素抵抗
TOLL样受体2
巨噬细胞极化
insulin resistance(IR)
Toll-like receptor 2(TLR2)
macrophage polarization
