40 YEARS of IGF1: Understanding the tissue-specific roles of IGF1/IGF1R in regulating metabolism using the Cre/loxP system.
40 YEARS of IGF1: Understanding the tissue-specific roles of IGF1/IGF1R in regulating metabolism using the Cre/loxP system.
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DOI：
10.1530/jme-18-0076
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发表时间：
2018-07
影响因子：
3.5
通讯作者：
Sarmento-Cabral A
中科院分区：
文献类型：
--
作者：
Kineman RD;Del Rio-Moreno M;Sarmento-Cabral A
很明显，IGF 1在支持生长和调节代谢方面很重要。在循环中发现的IGF 1主要由肝细胞产生，但健康的成熟肝细胞不表达可感知水平的IGF 1受体（IGF 1 R）。因此，认为IGF 1的代谢作用是通过肝细胞外作用介导的。由于IGF 1/IGF 1 R和胰岛素受体（INSR）信号传导之间的结构和功能同源性，以及IGF 1、IGF 1 R和INSR在身体的大多数组织中表达的事实，很难分离出IGF 1/IGF 1 R在维持全身代谢功能中的组织特异性贡献。为了解决这个问题，在过去的20年里，研究人员利用Cre/loxP系统以组织依赖性方式操纵IGF 1/IGF 1 R，最近以年龄依赖性方式操纵IGF 1/IGF 1 R。这些研究表明，IGF 1/IGF 1 R可以改变肝细胞外功能，以调节肝脏的激素输入和/或改变组织特异性碳水化合物和脂质代谢，以改变肝脏的营养流量，其中这些作用并不相互排斥，而是用于整合所有组织的功能，以支持生物体的代谢需求。
It is clear that IGF1 is important in supporting growth and regulating metabolism. The IGF1 found in the circulation is primarily produced by the liver hepatocytes, but healthy mature hepatocytes do not express appreciable levels of the IGF1 receptor (IGF1R). Therefore, the metabolic actions of IGF1 are thought to be mediated via extra-hepatocyte actions. Given the structural and functional homology between IGF1/IGF1R and insulin receptor (INSR) signaling, and the fact that IGF1, IGF1R and INSR are expressed in most tissues of the body, it is difficult to separate out the tissue-specific contributions of IGF1/IGF1R in maintaining whole body metabolic function. To circumvent this problem, over the last 20 years investigators have taken advantage of the Cre/loxP system to manipulate IGF1/IGF1R in a tissue-dependent, and more recently an age-dependent fashion. These studies have revealed that IGF1/IGF1R can alter extra-hepatocyte function to regulate hormonal inputs to the liver and/or alter tissue-specific carbohydrate and lipid metabolism to alter nutrient flux to liver, where these actions are not mutually exclusive, but serve to integrate the function of all tissues to support the metabolic needs of the organism.