烟酰胺核苷酸转氢酶基因在葡萄糖和能量代谢中的作用研究
发布时间：2019-06-03 05:34
【摘要】：缺失突变Nnt基因的C57BL/6J(B6J)小鼠广泛应用于葡萄糖耐受不良症的代谢研究。该基因在葡萄糖代谢和能量代谢中发挥重要作用。研究表明缺失Nnt基因的B6J小鼠其胰岛素分泌减少,线粒体活性氧增加。本研究中,对比分析了缺失Nnt基因的B6J小鼠和含完整Nnt基因的Km小鼠的血糖水平,并研究了Nnt基因对小鼠生长、饲料转化率性状的影响,得到如下结果:1.进化分析结果表明Nnt基因在多个物种间保守;猪、牛、羊、狗、马饲养家动物的Nnt基因同源性很高;然而,鸡Nnt基因与哺乳动物同源性相对较低。2.发现两个品系的小鼠在喂食后血糖水平均逐渐下降,并在空腹24h后达到最低水平。同时发现,喂食后空腹0h、2h、10h、24h B6J小鼠的血糖水平显著高于Km小鼠。3.构建了B6J×Km F2群体(N=342)。在该群体中,饥饿0到12h的Nnt-/-(缺失Nnt基因)纯合子小鼠的血糖变化程度要显著高于Nnt+/+型(含完整Nnt基因)纯合子小鼠(P0.05),Nnt+/-型小鼠的血糖水平与其它两种基因型小鼠无显著差异。4.B6J和Km小鼠在5周龄时在体重上呈现显著差异,但是在三周龄时体重差异不显著。5.利用F2群体对Nnt基因和代谢、生长、饲料转化率(feed conversion ratio,FCR)性状进行了关联分析,发现Nnt基因与3周龄体重(P0.01)、5周龄体重(P0.05)和平均代谢体重(P0.01)显著关联;与平均日采食量、平均日增重、FCR性状无显著关联。6.在F2群体中高FCR和低FCR小鼠的血糖水平差异不显著。7.QRT-PCR结果表明Nnt基因在肠道、心脏、肝脏和骨骼肌组织中高表达。在高FCR和低FCR的小鼠中Nnt、Glut-4和Igf-1基因的表达水平在肝脏组织中差异不显著。8.F2群体中高FCR小鼠的Glut-1和Ucp-2基因在肝脏中的表达水平显著高于低FCR小鼠(P0.05)。低FCR小鼠的Akt-1、Glut-2、Irs-1基因在肝脏中的表达水平显著高于高FCR小鼠(P0.05)。9.C2C12细胞中存在Nnt基因的表达,但是在分化过程中该基因的表达水平差异不显著。10.双荧光素酶报告基因检测结果发现,Nnt基因受到miR-221、miR-222调控。以上结果说明在小鼠中Nnt基因参与调控血糖稳定、基础能量代谢和生长性状存在关联,但不影响其饲料效率性状。另外,Nnt基因可能受到miR-221、miR-222转录后调控。这些研究结果为解释Nnt基因在代谢和生长中的作用提供了新的依据。
[Abstract]:C57BL/6J (B6J) mice with deletion mutation Nnt gene are widely used in the metabolism of glucose tolerance. The gene plays an important role in glucose metabolism and energy metabolism. The results showed that the insulin secretion of B6J mice without Nnt gene decreased and the activity of reactive oxygen species (Ros) increased. In this study, the blood glucose levels of B6J mice without Nnt gene and Km mice containing complete Nnt gene were compared and analyzed, and the effects of Nnt gene on the growth and feed conversion rate of mice were studied. the results were as follows: 1. The results of evolutionary analysis showed that the Nnt gene was conserved among many species; the homology of Nnt gene in pigs, cattle, sheep, dogs and horse breeders was very high; however, the homology between chicken Nnt gene and mammals was relatively low. It was found that the blood glucose level of the two strains of mice decreased gradually after feeding, and reached the lowest level after 24 hours on an empty stomach. At the same time, it was found that the blood glucose level of 24 h B6J mice was significantly higher than that of Km mice at 0 h, 2 h and 10 h after feeding. The B6J 脳 Km F2 population (N 鈮，
本文编号：2491712
[Abstract]:C57BL/6J (B6J) mice with deletion mutation Nnt gene are widely used in the metabolism of glucose tolerance. The gene plays an important role in glucose metabolism and energy metabolism. The results showed that the insulin secretion of B6J mice without Nnt gene decreased and the activity of reactive oxygen species (Ros) increased. In this study, the blood glucose levels of B6J mice without Nnt gene and Km mice containing complete Nnt gene were compared and analyzed, and the effects of Nnt gene on the growth and feed conversion rate of mice were studied. the results were as follows: 1. The results of evolutionary analysis showed that the Nnt gene was conserved among many species; the homology of Nnt gene in pigs, cattle, sheep, dogs and horse breeders was very high; however, the homology between chicken Nnt gene and mammals was relatively low. It was found that the blood glucose level of the two strains of mice decreased gradually after feeding, and reached the lowest level after 24 hours on an empty stomach. At the same time, it was found that the blood glucose level of 24 h B6J mice was significantly higher than that of Km mice at 0 h, 2 h and 10 h after feeding. The B6J 脳 Km F2 population (N 鈮，
本文编号：2491712
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