驱动蛋白-1在小鼠脂肪组织糖脂代谢中的作用研究

目的:本文旨在探讨动物体内水平驱动蛋白-1在脂肪组织糖、脂代谢中的作用。方法:通过Cre/Loxp重组系统构建脂肪组织特异性敲除驱动蛋白-1的小鼠模型,在生理水平观察驱动蛋白-1表达缺陷对小鼠糖代谢、脂代谢和脂肪因子分泌的影响。结果:与六月龄对照组小鼠相比,同月龄驱动蛋白-1敲除小鼠的体重、脂肪组织重量和空腹血糖水平没有显著差异,但是其血清胰岛素水平显著升高;使用葡萄糖耐量试验(GTT)和胰岛素耐量实验(ITT)对小鼠的糖代谢水平进行评估,结果显示驱动蛋白-1敲除小鼠表现为葡萄糖不耐受、胰岛素不耐受;进一步血清检测显示驱动蛋白-1敲除小鼠表现为高甘油三酯血症和血清脂联素水平降低。结论:驱动蛋白-1在脂肪组织中参与调节糖、脂代谢过程,其表达或功能障碍是2型糖尿病等代谢性疾病的一个重要的发病因素。

Functional Study of Kinesin-1 on Glucose and Lipid Metabolism in Adipose of C57BL/6 Mouse

ABSTRACT Objective: Kinesin-1 is a microtubule plus-end directed motor protein, which serve as vehicles to mediate cargo transportation in cells. In vitro studies have shown that Kinesin-1 mediates glucose transporter type 4 translocation and adiponectin secretion in adipocytes. To investigate the possible roles of Kinesin-1 in vivo, the physiological functions of Kinesin-1 in adipose were examined in a conditional knockout out mouse model. Methods: Adipose specific Kinesin-1 knockout mice were generated by Cre/Loxp recombinant system. Glucose tolerance, insulin tolerance, serum lipids and adipokine levels were examined in Kinesin-1 knockout mice as well as littermate controls. Results: Compared with the control mice, the Kinesin-1 knockout mice had comparable body weight, adipose tissue weight, fast blood glucose level and higher serum insulin level. Glucose tolerance test (GTT) and insulin tolerance test (ITT) were used to evaluate the glucose metabolism level. The Kinesin-1 knockout mice showed glucose intolerance and insulin intolerance. Serum examination further revealed that the Kinesin-1 knockout mice hadhypertriglyceridemia and decreased serum adiponectin levels. Conclusion: Kinesin-1 is involved in the glucose and lipid metabolism in adipose tissue, its expressional or functional defect is an important risk factor for metabolic diseases such as type 2 diabetes mellitus.