High lipoprotein lipase activity increases insulin sensitivity in transgenic rabbits
High lipoprotein lipase activity increases insulin sensitivity in transgenic rabbits
复制标题
DOI：
10.1016/j.metabol.2004.07.021
复制
发表时间：
2005-01-01
影响因子：
9.8
通讯作者：
Fan, JL
中科院分区：
文献类型：
--
作者：
Liu, EQ;Kitajima, S;Fan, JL
脂蛋白脂酶（LPL）是水解富含磷脂酰肌醇脂蛋白的限速酶，在糖代谢中起重要作用。为了检验LPL活性增加可能改变胰岛素敏感性的假设，我们研究了在β-肌动蛋白启动子控制下表达人LPL基因的转基因（Tg）兔的葡萄糖代谢和胰岛素敏感性。静脉葡萄糖耐量试验显示，Tg和非Tg兔之间的血糖清除率无显著差异;然而，Tg兔的胰岛素和游离脂肪酸曲线下面积与非Tg兔相比显著降低（P <0.05）。静脉胰岛素耐量试验发现，Tg家兔的血糖曲线下面积也明显减小（P <0.01）。正常血糖-高胰岛素钳夹试验显示，Tg兔的平均葡萄糖输注速率显著高于非Tg兔（P <0.05）。这些结果表明，LPL的系统性过表达增加全身胰岛素敏感性，LPL基因的遗传操作可能是治疗糖尿病患者的潜在靶点。(c)2004年爱思唯尔公司All rights reserved.
Lipoprotein lipase (LPL) is the rate-limiting enzyme in the hydrolysis of triglyceride-rich lipoproteins and plays an important role in glucose metabolism. To examine the hypothesis that increased LPL activity may alter insulin sensitivity, we investigated glucose metabolism and insulin sensitivity in transgenic (Tg) rabbits expressing the human LPL gene under the control of a beta-actin promoter. An intravenous glucose tolerance test showed that the plasma glucose clearance rate was not significantly different between Tg and non-Tg rabbits; however, the area under the curve for insulin and free fatty acids in Tg rabbits was significantly reduced compared with that of non-Tg rabbits (P < .05). Using the intravenous insulin tolerance test, we found that the area of under the curve of glucose of Tg rabbits was also significantly reduced (P < .01). Furthermore, euglycemic-hyperinsulinemic clamp test revealed that the mean glucose infusion rate in Tg rabbits was significantly higher than in non-Tg rabbits (P < .05). These results demonstrate that systemic overexpression of LPL increases whole-body insulin sensitivity and genetic manipulation of LPL genes may be a potential target for the treatment of diabetic patients. (c) 2004 Elsevier Inc. All rights reserved.