mTORC1 signaling and regulation of pancreatic β-cell mass
mTORC1 signaling and regulation of pancreatic β-cell mass
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DOI：
10.4161/cc.20036
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发表时间：
2012-05-15
期刊：
影响因子：
4.3
通讯作者：
Bernal-Mizrachi, Ernesto
中科院分区：
文献类型：
--
作者：
Blandino-Rosano, Manuel;Chen, Angela Y.;Bernal-Mizrachi, Ernesto
β细胞响应胰岛素抵抗而扩增的能力是2型糖尿病发展的关键因素。β细胞的增殖是动物模型中这些适应性反应的主要组成部分。负责β细胞扩增的细胞外信号包括生长因子，如胰岛素，和营养素，如葡萄糖和氨基酸。AKT激活是将生长信号与β细胞扩增调节联系起来的重要组成部分之一。在AKT的下游，结节性硬化症复合物1和2（TSC 1/2）和雷帕霉素复合物1（mTORC 1）信号传导的机制靶标已经成为这一过程中的主要候选者，因为它们整合了来自生长因子和营养素的信号。最近的研究表明mTORC 1信号在β细胞中的重要性。这篇综述将讨论最近的进展，了解这一途径如何调节β细胞质量和目前的数据TSC 1在β细胞质量的调制中的作用。在此，我们还证明了胰腺β细胞中Tsc 1的缺失导致葡萄糖耐量改善，高胰岛素血症和β细胞群的扩张，这些都随着年龄的增长而持续存在。
The capacity of beta cells to expand in response to insulin resistance is a critical factor in the development of type 2 diabetes. Proliferation of beta cells is a major component for these adaptive responses in animal models. The extracellular signals responsible for beta-cell expansion include growth factors, such as insulin, and nutrients, such as glucose and amino acids. AKT activation is one of the important components linking growth signals to the regulation of beta-cell expansion. Downstream of AKT, tuberous sclerosis complex 1 and 2 (TSC1/2) and mechanistic target of rapamycin complex 1 (mTORC1) signaling have emerged as prime candidates in this process, because they integrate signals from growth factors and nutrients. Recent studies demonstrate the importance of mTORC1 signaling in beta cells. This review will discuss recent advances in the understanding of how this pathway regulates beta-cell mass and present data on the role of TSC1 in modulation of beta-cell mass. Herein, we also demonstrate that deletion of Tsc1 in pancreatic beta cells results in improved glucose tolerance, hyperinsulinemia and expansion of beta-cell mass that persists with aging.