ATGL／HSL角度下解析Neu-p11改善胰岛素抵抗作用机制  

Neu-p11 ameliorates insulin resisitance in 3T3-L1 adipocytes based on ATGL/HSL and its underlying mechanism

作　　者：王平平[1] 佘美华[2] Laudon Moshe 尹卫东[1,2] 

机构地区：[1]南华大学心血管疾病研究所,湖南衡阳421001 [2]南华大学生物化学与分子生物学系,湖南衡阳421001 [3]Neunm Pharmaceuticals Ltd.,以色列

出　　处：《中国药理学通报》2013年第6期793-796,共4页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81270269,81200590,B2012-043)

摘　　要：目的探讨脂肪组织甘油三酯酶(adipose triglyceridelipase,ATGL)及激素敏感性脂肪酶(hormone-sensitive lipase,HSL)在褪黑素非选择性受体激动剂Neu-p11改善高糖高胰岛素(high glucose and insulin,HGI)诱导的3T3-L1脂肪细胞胰岛素抵抗(insulin resistance,IR)中的作用及机制。方法培养3T3-L1脂肪细胞,HGI诱导IR模型。以葡萄糖消耗量及细胞内甘油三酯(triglyceride,TG)定量测定作为检测指标,Western blot检测蛋白水平的表达情况。结果 HGI孵育减少脂肪细胞葡萄糖摄取,促进细胞内TG积聚,同时伴有ATGL及HSL的蛋白表达下调。Neu-p11干预逆转了HGI对脂肪细胞的作用效应,而MT2竞争性拮抗剂luzindole却拮抗了Neu-p11的上述效应。结论 Neu-p11以MT2受体依赖性方式抑制IR脂肪细胞TG沉积,可能与其上调AT-GL、HSL蛋白的表达,促进TG水解相关。Aim To explore the possible role of adi- pose tissue triglyceride enzyme （ATGL） and hormone-sensitive lipase （HSL） in high glucose and insulin （ HGI ） - induced insulin resistance in 3T3-L1 adipo-cytes and the underlying mechanisms. Methods 3T3- L1 adipocytes were administered with HGI for 24 h to induce insulin resistance. Glucose uptake and the quantitative determination of triglycerides were de- signed for detection indicators. Protein expressions were detected by Western blot. Results HGI incuba- ting resulted in decreased insulin-stimulated glucose uptake and a significant increase in TG content in fat cells, with a concomitant decrease in ATGL and HSLprotein expression. The Neu-pll intervention reversed the effects of HGI on fat cells, while luzindole counter- acted the effect of Neu-pll. Conclusions Neu-pll might inhibit TG deposition in insulin-resistant 3T3-L1 adipocytes via MT2 receptor -dependent manner, at least in part by increasing triglyceride hydrolysis, re- suiting from enhancing ATGL and HSL levels.

关 键 词：Neu-p11 胰岛素抵抗 甘油三酯 脂肪组织甘油三酯 酶 激素敏感性脂肪酶 CA2+ LUZINDOLE 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学] R344.3[医药卫生—基础医学]