...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >Essential Role of Insulin Receptor Substrate 1 in Differentiation of Brown Adipocytes
【24h】

Essential Role of Insulin Receptor Substrate 1 in Differentiation of Brown Adipocytes

机译：胰岛素受体底物1在棕色脂肪细胞分化中的重要作用

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

The most widely distributed members of the family of insulin receptor substrate (IRS) proteins are IRS-1 and IRS-2. These proteins participate in insulin and insulin-like growth factor 1 signaling, as well as the actions of some cytokines, growth hormone, and prolactin. To more precisely define the specific role of IRS-1 in adipocyte biology, we established brown adipocyte cell lines from wild-type and IRS-1 knockout (KO) animals. Using differentiation protocols, both with and without insulin, preadipocyte cell lines derived from IRS-1 KO mice exhibited a marked decrease in differentiation and lipid accumulation (10 to 40%) compared to wild-type cells (90 to 100%). Furthermore, IRS-1 KO cells showed decreased expression of adipogenic marker proteins, such as peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT/enhancer-binding protein alpha (C/EBPα), fatty acid synthase, uncoupling protein-1, and glucose transporter 4. The differentiation deficit in the KO cells could be reversed almost completely by retrovirus-mediated reexpression of IRS-1, PPARγ, or C/EBPα but not the thiazolidinedione troglitazone. Phosphatidylinositol 3-kinase (PI 3-kinase) assays performed at various stages of the differentiation process revealed a strong and transient activation in IRS-1, IRS-2, and phosphotyrosine-associated PI 3-kinase in the wild-type cells, whereas the IRS-1 KO cells showed impaired phosphotyrosine-associated PI 3-kinase activation, all of which was associated with IRS-2. Akt phosphorylation was reduced in parallel with the total PI 3-kinase activity. Inhibition of PI 3-kinase with LY294002 blocked differentiation of wild-type cells. Thus, IRS-1 appears to be an important mediator of brown adipocyte maturation. Furthermore, this signaling molecule appears to exert its unique role in the differentiation process via activation of PI 3-kinase and its downstream target, Akt, and is upstream of the effects of PPARγ and C/EBPα.
机译：胰岛素受体底物（IRS）蛋白家族中分布最广的成员是IRS-1和IRS-2。这些蛋白质参与胰岛素和胰岛素样生长因子1信号传导，以及某些细胞因子，生长激素和催乳激素的作用。为了更准确地定义IRS-1在脂肪细胞生物学中的特定作用，我们从野生型和IRS-1敲除（KO）动物中建立了棕色脂肪细胞细胞系。使用分化方案，无论有无胰岛素，与野生型细胞（90％至100％）相比，源自IRS-1 KO小鼠的前脂肪细胞系均表现出分化和脂质蓄积的明显减少（10％至40％）。此外，IRS-1 KO细胞显示成脂标记蛋白（如过氧化物酶体增殖物激活受体γ（PPARγ），CCAAT /增强子结合蛋白α（C /EBPα），脂肪酸合酶，解偶联蛋白-1和葡萄糖转运蛋白4.逆转录病毒介导的IRS-1，PPARγ或C /EBPα的重新表达几乎可以完全逆转KO细胞中的分化缺陷，而噻唑烷二酮曲格列酮则不能。在分化过程的各个阶段进行的磷脂酰肌醇3激酶（PI 3激酶）分析显示，野生型细胞中IRS-1，IRS-2和磷酸酪氨酸相关的PI 3激酶具有强烈而短暂的激活，而IRS-1 KO细胞显示磷酸酪氨酸相关的PI 3激酶激活受损，所有这些都与IRS-2相关。与总的PI 3激酶活性平行地，降低了Akt磷酸化。 LY294002抑制PI 3-激酶可阻断野生型细胞的分化。因此，IRS-1似乎是褐色脂肪细胞成熟的重要介体。此外，该信号分子似乎通过激活PI 3-激酶及其下游靶标Akt在分化过程中发挥其独特作用，并且位于PPARγ和C /EBPα作用的上游。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号