糖尿病基础研究

　　【摘要】 目的 探讨胰升血糖素样肽-1(GLP-1)对内质网应激状态下脂肪细胞内脏脂肪素表达的调节作用。 方法 3T3-L1分化成熟的脂肪细胞，经Tg诱导建立内质网应激模型。脂肪细胞经Tg和/或GLP-1孵育后，收集细胞用于总RNA的提取，收集细胞液用于ELISA分析。定量PCR检测内脏脂肪素转录水平，ELISA检测其分泌水平。内质网应激发生通过测定sXBP-1表达水平增加来判断。使用细胞核因子κB(NF-κB)特异阻断剂PDTC预处理30 min，观察NF-κB在GLP-1调节内脏脂肪素表达中的作用。 结果 Tg诱导后sXBP-1表达增加，内脏脂肪素表达下降并呈剂量依赖性;同时给予GLP-1处理后，内脏脂肪素表达增加;PDTC降低内脏脂肪素基础水平，并未阻断GLP-1作用。 结论 GLP-1提升内质网应激状态下脂肪细胞内脏脂肪素的表达。

　　【关键词】 胰升血糖素样多肽-1;内脏脂肪素;脂肪细胞;糖尿病

　　【Abstract】Objective To investigate whether glucagon like peptide-1 (GLP-1) would regulate the expression of visfatin in adipocytes following endoplasmic reticulum stress and to explore the mechanism of this effect. Methods Fully differentiated 3T3-L1 adipocytes were induced with thapsigargin (Tg) to develop endoplasmic reticulum stress (ER stress) model. After treated with Tg together with or without GLP-1, the adipocytes were harvested for total RNA extraction, and the cellular fluid was collected for ELISA analysis. The level of visfatin transcripts was analyzed by quantitative RT-PCR with gene-specific primers. The level of visfatin protein in media was measured by enzyme linked immunoassay (ELISA). And endoplasmic reticulum stress (ER stress) was confirmed through determining the expression level of sXBP-1. In order to test the involvement of NF-κB, the adipocytes were pretreated with a specific pharmacological NF-κB inhibitor PDTC and then GLP-1 was added. Results Tg incubation increased the sXBP-1 level and decreased the visfatin expression in a dose-dependent manner. Meanwhile, GLP-1 moderately reversed this negative effect of Tg on visfatin. PDTC reduced the basal level of visfatin expression,while did not block the effect of GLP-1 on visfatin. Conclusion GLP-1 enhanced the expression of visfatin in3T3-L1 adipocyte following ER stress, which might contributes to the improvement effect of GLP-1 on glucose homeostasis.

　　【Key words】Glucagon like peptide-1;Visfatin;Adipocyte;Diabetes