JBC：Ⅱ型糖尿病胰岛素抵抗两相关基因
美国阿拉巴马大学（UAB）研究人员鉴定出与胰岛素抵抗相关两基因——NR4A3 和NR4A1，从而为Ⅱ型糖尿病和其他代谢综合征的治疗提供了一条新途径。研究结果发表在10 月26 日Journal of Biological Chemistry上。
胰岛素通过将血糖从血管中移动到骨骼肌用于能量代谢或者储存下来随后利用的方式，来降低血糖。Ⅱ型糖尿病的发生源于胰岛素缺乏，或者是肌肉钝化，不能响应胰岛素信号，从而导致血液中葡萄糖含量的升高。第二种情形，即不能对胰岛素信号做出响应称之为胰岛素抵抗（insulin resistance）。
UAB 营养科学系主任，论文作者W. Timothy Garvey 教授称，这两个蛋白可以促使肌肉对胰岛素敏感，加速葡萄糖的摄取，从而维持正常的血糖水平。研究同时发现，在动物糖尿病模型中，两个基因表达下调，伴随胰岛素抵抗提高。
对糖尿病研究而言，新的发现提示可以以提升NR4A3 和NR4A1 表达或活性进行药物研发。Garvey 表示，下一步工作将围绕可以与两个蛋白相互作用或者促进其表达的分子的筛选。
目前，美国目前有2 千万糖尿病患者，占总人口的7%。美国国立卫生研究院（NIH）称，随着美国人口的老龄化和美国人群中肥胖的盛行，糖尿病的发病率可能进一步增加。
王小理 编译自http://www.sciencedaily.com/releases/2007/10/071027095416.htm
原始出处:
J. Biol. Chem., Vol. 282, Issue 43, 31525-31533, October 26, 2007
1
From the Department of Nutrition Sciences, University of Alabama at Birmingham, Birmingham, Alabama 35294-3360 and the Birmingham Veterans Affairs Medical Center, Birmingham, Alabama 35233
After observing that expression of two NR4A orphan nuclear receptors, NR4A3 and NR4A1, was altered by insulin in cDNA microarray analyses of human skeletal muscle, we studied whether these receptors could modulate insulin sensitivity. We found that both NR4A3 and NR4A1 were induced by insulin and by thiazolidinedione drugs (pioglitazone and troglitazone) in 3T3-L1 adipocytes. Furthermore, gene expression of NR4A3 and NR4A1 was reduced in skeletal muscles and adipose tissues from multiple rodent models of insulin resistance. To determine whether NR4A3 could modulate insulin sensitivity, 3T3-L1 adipocytes were stably transduced with NR4A3 or LacZ (control) lentiviral vectors. Compared with LacZ expressing cells, hyperexpression of NR4A3 increased the ability of insulin to augment glucose transport activity, and the mechanism involved increased recruitment of GLUT4 glucose transporters to the plasma membrane. NR4A3 hyperexpression also led to an increase in insulin-mediated tyrosine phosphorylation of insulin receptor substrate-1 as well as Akt phosphorylation. Suppression of NR4A3 using lentiviral short hairpin RNA constructs reduced the ability of insulin to stimulate glucose transport and phosphorylate Insulin receptor substrate-1 and Akt. Thus, NR4A3 and NR4A1 are attractive novel therapeutic targets for potential amelioration of insulin resistance, and treatment and prevention of type 2 diabetes and the metabolic syndrome.
相关报道:
| 苯扎贝特减弱冠状动脉疾病患者的胰岛素抵抗 |
- 众说风云 (已有0条评论)
