Neu-p11/Luzindole在胰岛素抵抗脂肪细胞模型中对脂联素/内脏脂肪素的影响  

Effect of Neu-p11/Luzindole on Expression of Adiponectin/Visfatin in Insulin Resistance Adipocytes Model

作　　者：李秀平[1] 蔡世昌[1] 尹卫东[2] 胡晓波[2] Moshe Laudon 

机构地区：[1]湖南怀化医学高等专科学校,湖南怀化418000 [2]南华大学医学院心血管疾病研究所,湖南衡阳412000 [3]Neurim Pharmaceuticals Ltd.

出　　处：《生物物理学报》2013年第6期422-432,共11页Acta Biophysica Sinica

基　　金：湖南省教育厅科学研究项目(12C1196);怀化医专科学研究项目(2011KY03)~~

摘　　要：脂联素(adiponectin)在调节胰岛素敏感性和葡萄糖的内稳态方面发挥着至关重要的作用,与胰岛素抵抗密切相关;内脏脂肪素(visfatin)可与胰岛素受体相互作用,发挥类胰岛素或抗胰岛素样作用,从而降低血糖,其量的变化与胰岛素抵抗的发生也有着紧密的联系。通过"鸡尾酒"法培养并分化3T3-L1前脂肪细胞,油红O染色鉴定脂肪细胞的形态和分化情况,高糖高胰岛素作用于脂肪细胞,建立胰岛素抵抗细胞模型;葡萄糖氧化酶法测定培养基中的糖含量,计算糖消耗量,验证胰岛素抵抗模型的建立。葡萄糖氧化酶法检测药物作用前后培养基中的糖含量,计算糖消耗量;Western-blot检测药物作用前后脂联素和内脏脂肪素表达的变化,来研究Neu-P11改善高糖高胰岛素引起3T3-L1脂肪细胞发生胰岛素抵抗的机制,以及葡萄糖摄取和脂联素及内脏脂肪素的变化;探讨褪黑素受体拮抗剂Luzindole与Neu-P11联合作用后,对葡萄糖摄取及脂联素和内脏脂肪素表达的影响。结果表明,高糖高胰岛素作用于分化成熟的脂肪细胞24 h后,糖消耗量与正常对照组细胞相比明显降低,其胰岛素敏感性也随之下降;胰岛素抵抗组细胞用褪黑素和Neu-P11处理后,糖消耗量与未处理组相比明显升高,胰岛素敏感性也随之上升;脂联素表达明显增高,与未处理组相比,差异有统计学意义;内脏脂肪素表达变化不明显,与未处理组相比,差异没有统计学意义。褪黑素、Neu-P11分别与褪黑素受体拮抗剂Luzindole联合作用于细胞后,细胞的脂联素表达水平与未加拮抗剂Luzindole的褪黑素、Neu-P11组相比明显下降,差异具有统计学意义,与未处理组相比,没有明显变化,差异没有统计学意义。因此,褪黑素和Neu-P11都可提高胰岛素抵抗脂肪细胞的胰岛素敏感性,增加糖消耗量,使脂联素表达上调,而对内脏脂肪素表达没有明显影响;褪黑素和Neu-P11可能是通过�Adiponectin plays a vital role in the regulation of insulin sensitivity and glucose homeostasis, and is closely related to insulin resistance. Visfatin can interact with the insulin receptor, playing a para-insulin or anti-insulin effect, so as to reduces blood glucose. Its quantitative change of volume also has tight correlation with insulin resistance. 3T3-L1 pre-adipocytes were cultivated and differentiated in adipogenic cocktail containing isobutyl-l-methyl xanthine （IBMX）, dexamethasone （DEX） and insulin; the morphology and differentiation of adipocytes were identified by oil red O staining; High glucose/ insulin acted on adipocytes to establish insulin resistance cells model; glucose content in culture medium was measured by glucose oxidase method and glucose consumption was calculated to confirm the establishment of insulin resistance model. The changes of adiponectin and visfatin protein expressions before and after drug action were detected by Western blot to study the mechanism of Neu-P11＇s effect on improving high glucose/ insulin and causing 3T3-L1 adipose cells＇ insulin resistance; the combined effects of melatonin receptor antagonist Luzindole and Neu-P11 on glucose uptake and the expressions of adiponectin and visfatin protein were probed. The research indicates that 24 h after the action of high glucose/ insulin on differentiated and matured adipocytes, the glucose assumption decreased dramatically compared with that of the cells of controlled group, and insulin sensitivity also decreased thereupon. After treated by melatonin and Neu-P11, the glucose consumption of the cells in insulin resistance group increased obviously, compared with those in IR group, and the insulin sensitivity also increased accordingly. The expression of adiponectin protein increased dramatically compared with IR group, and the change had statistical significance. The change of the expression of visfatin protein was not obvious, and had no statistical significance compared with IR group. After the respective com

关 键 词：Neu P11 褪黑素 高糖高胰岛素 3T3-L1细胞 脂联素 内脏脂肪素 胰岛素抵抗 LUZINDOLE 

分 类 号：Q251[生物学—细胞生物学]