Exendin-4可通过下调内质网应激信号标志蛋白表达改善3T3-L1脂肪细胞的胰岛素抵抗

发布时间：2018-05-24 21:56

本文选题：Exendin- + 内质网应激　；参考：《中国病理生理杂志》2017年07期

【摘要】：目的:探讨胰高血糖素样肽-1(GLP-1)受体激动剂exendin-4对内质网应激(ERS)诱导剂衣霉素(TM)介导的3T3-L1脂肪细胞胰岛素抵抗(IR)的影响。方法:体外培养3T3-L1脂肪细胞,分别用TM、内质网应激抑制剂牛磺熊脱氧胆酸(TUDCA)及exendin-4进行干预,以MTT法检测不同干预条件下脂肪细胞的存活情况,以葡萄糖氧化酶法检测不同干预条件下脂肪细胞的葡萄糖消耗量情况,利用Western blot法检测不同干预条件下p-Akt、Akt及ERS关键信号标志蛋白肌醇需求蛋白1(IRE1)、p-IRE1、c-Jun末端激酶(JNK)、p-JNK、蛋白激酶R样内质网激酶(PERK)、p-PERK、真核生物翻译起始因子2的α亚单位(eIF2a)、p-eIF2a和转录激活因子(ATF)-6的蛋白水平。结果:单独TUDCA或exendin-4作用,可协同胰岛素作用,增加胰岛素刺激的脂肪细胞葡萄糖消耗量(P0.05)。TM(5 mg/L)作用5 h后可减少胰岛素刺激的3T3-L1脂肪细胞萄糖消耗量(P0.05)及p-Akt的蛋白水平(P0.05)。TUDCA(1 mmol/L)或exendin-4(100 nmol/L)预处理24 h后,均可拮抗TM对胰岛素刺激的3T3-L1脂肪细胞萄糖消耗量(P0.05)及p-Akt蛋白水平的改变(P0.05),二者效价相当。TM(5 mg/L)作用5 h后可显著提高ERS标志蛋白的表达。而exendin-4(100 nmol/L)预处理24 h后,可降低TM诱导的ERS标志蛋白的表达,其效价与应用内质网应激抑制剂TUDCA(1 mmol/L)预处理24 h相当。不同的处理因素对于总IRE1、JNK、PERK及eIF2a的表达情况并无显著性影响。结论:Exendin-4可改善内质网应激介导的3T3-L1脂肪细胞的胰岛素抵抗。
[Abstract]:Aim: to investigate the effect of glucagon-like peptide-1 (GLP-1) receptor agonist exendin-4 on insulin resistance of 3T3-L1 adipocytes induced by endoplasmic reticulum stress (ERS) inducer. Methods: 3T3-L1 adipocytes were cultured in vitro and treated with TMN, endoplasmic reticulum stress inhibitor TUDCA and exendin-4, respectively. The survival of adipocytes under different intervention conditions was detected by MTT method. Glucose consumption of adipocytes was measured by glucose oxidase method under different intervention conditions. Western blot assay was used to detect the inositol requirements protein (IRE1), a key signal marker protein of p-Akt and ERS, in different intervention conditions, and transcriptional stimulation. The protein kinase R-like endoplasmic reticulum kinase (PERKK) p-PERK, the 伪 subunit of eukaryote translation initiation factor 2, eIF2a, and transcriptional excitations were detected. The protein level of ATF- 6. Results: TUDCA or exendin-4 alone could cooperate with insulin. Increased glucose consumption of adipocytes stimulated by insulin (P0.05N 路TMN 5mg / L) decreased glucose consumption of insulin-stimulated 3T3-L1 adipocytes (P0.05) and protein levels of p-Akt (P0.05N 路TUDCA1 mmol / L) or exendin-4(100 nmol / L) for 24 h. The changes of glucose consumption and p-Akt protein level of insulin stimulated 3T3-L1 adipocytes were antagonized by TM. The titer of them was the same. TMN 5 mg / L could significantly increase the expression of ERS marker protein after 5 h treatment. After pretreatment with exendin-4(100 nmol / L for 24 h, the expression of ERS marker protein induced by TM was reduced, and its titer was similar to that of pretreatment with endoplasmic reticulum stress inhibitor TUDCA(1 mmol / L for 24 h. Different treatment factors had no significant effect on the expression of total IRE1 JNKPERK and eIF2a. Conclusion 1: Exendin-4 can improve insulin resistance of 3T3-L1 adipocytes mediated by endoplasmic reticulum stress.
【作者单位】：福建医科大学附属协和医院内分泌科福建省内分泌研究所;福建医科大学附属协和医院老年病科;福建医科大学药学院;福建医科大学老年健康科学研究院;
【基金】：福建省科技重点项目(No.2013Y0041) 福建省卫生厅青年课题(No.2009-2-24) 国家重点学科老年医学项目资助(No.2015-GJLN-2-04) 福建省卫计委青年项目(No.2014-1-43;No.2015-1-38)
【分类号】：R587.1

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