内质网应激与肝脏胰岛素抵抗

肝脏是机体物质代谢的中心,也是胰岛素作用的重要靶器官。肝脏胰岛素抵抗会影响糖脂代谢,机体出现血糖升高、肝内脂质沉积等症状,从而进一步加重胰岛素抵抗,二者形成恶性循环。内质网是蛋白质合成、折叠、加工及其质量监控的重要场所,广泛分布于真核细胞中。当机体出现生理性应激(如蛋白质分泌量增加)或病理性应激(如内质网中存在大量无法正确折叠的突变蛋白质)时,会导致蛋白质折叠需求与内质网蛋白质折叠能力之间的不平衡,从而引起内质网应激。内质网应激与肝脏胰岛素抵抗密切相关。近年来,大量研究发现,内质网应激不仅能直接破坏胰岛素信号传导通路,还可以通过多种方式作用于靶组织进一步促进胰岛素抵抗(尤其在肝脏)。

Endoplasmic reticulum stress and hepatic insulin resistance

Liver is the center of material metabolism and an important target organ for insulin action.Hepatic insulin resistance(IR)can affect the metabolism of glucose and lipid,which eventually leads to elevated blood glucose and lipid deposition in liver,which will further aggravate IR,forming a vicious circle.Endoplasmic reticulum(ER)is an important site for protein synthesis,folding,processing and quality-monitoring.It is widely distributed in eukaryotic cells.When physiological stress(such as increased protein secretion)or pathological stress(such as large number of mutated proteins in the ER can not fold properly)occurs,the imbalance between protein folding requirements and protein folding capacity of the ER will result in endoplasmic reticulum stress(ER stress).ER stress is closely related to IR.In recent years,a large number of studies have found that ER stress can not only directly damage the insulin signaling pathway,but also further promote IR in a variety of ways to act on the target tissues,especially in liver.