Comparison of in vivo effects of insulin on SREBP-1c activation and INSIG-1/2 in rat liver and human and rat adipose tissue.
Comparison of in vivo effects of insulin on SREBP-1c activation and INSIG-1/2 in rat liver and human and rat adipose tissue.
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胰岛素对大鼠肝脏，人和大鼠脂肪组织中胰岛素对SREBP-1C激活和Insig-1/2的体内影响的比较。
DOI：
10.1002/oby.20134
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发表时间：
2013-06
期刊：
影响因子：
6.9
通讯作者：
Jayarajan, Senthil
中科院分区：
文献类型：
--
作者：
Boden, Guenther;Salehi, Sajad;Cheung, Peter;Homko, Carol;Song, Weiwei;Loveland-Jones, Catherine;Jayarajan, Senthil
胰岛素对肝脏中新生脂肪生成（DNL）的刺激作用很强且已得到充分证实，胰岛素是非酒精性脂肪肝病（NAFLD）、肝脏和全身胰岛素抵抗的重要促成因素。相比之下，胰岛素在脂肪组织中的DNL中仅起次要作用。胰岛素在肝脏中比在脂肪中更能刺激DNL的原因尚不清楚，但可能是由于固醇调节元件结合蛋白（SREBP）的转录和翻译后激活的差异调节。为了验证这一假设，我们研究了胰岛素对大鼠肝脏以及大鼠和人类受试者脂肪组织中SREBP-1c活化的影响。从警觉大鼠获得肝脏和脂肪，并从人类受试者的皮下脂肪组织中获得对4 h正常血糖-高胰岛素钳夹的反应。在这里，我们发现，在大鼠和人类中，急性升高血浆胰岛素水平使大鼠肝脏和大鼠及人类脂肪组织中的SREBP-1 mRNA增加了约3-4倍，但仅在大鼠肝脏中增加了SREBP-1c的翻译后激活，而在脂肪组织中减少了SREBP-1c。胰岛素对肝脏和脂肪组织中SREBP-1c活化的这些差异效应与INSIG-1相反方向的稳健变化相关，而INSIG-2 mRNA和蛋白的变化程度较低。我们的结论是，这些发现支持了胰岛素刺激肝脏中SREBP-1c激活的假设，至少部分是通过抑制INSIG-1和-2，而在脂肪组织中，INSIG-1和-2的增加阻止了SREBP-1c的激活。
The stimulatory effects of insulin on de novo lipogenesis (DNL) in the liver, where it is an important contributor to non-alcoholic fatty liver disease (NAFLD), hepatic and systemic insulin resistance, is strong and well established. In contrast, insulin plays only a minor role in DNL in adipose tissue. The reason why insulin stimulates DNL more in liver than in fat is not known but may be due to differential regulation of the transcription and post-translational activation of sterol regulatory element binding proteins (SREBPs). To test this hypothesis, we have examined effects of insulin on activation of SREBP-1c in liver of rats and in adipose tissue of rats and human subjects. Liver and epidydimal fat were obtained from alert rats and subcutaneous adipose tissue from human subjects in response to 4 h euglycemic-hyperinsulinemic clamps. Here we show that acutely raising plasma insulin levels in rats and humans increased SREBP-1 mRNA comparably 3-4 fold in rat liver and rat and human adipose tissue, but increased post-translational activation of SREBP-1c only in rat liver, while decreasing it in adipose tissue. These differential effects of insulin on SREBP-1c activation in liver and adipose tissue were associated with robust changes in the opposite direction of INSIG-1 and to a lesser extent of INSIG-2 mRNA and proteins. We conclude that these findings support the hypothesis that insulin stimulated activation of SREBP-1c in the liver, at least in part, by suppressing INSIG-1 and -2, whereas in adipose tissue, an increase in INSIG-1 and -2 prevented SREBP-1c activation.
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DOI：
10.1073/pnas.0401715101
发表时间：
2004-05-04
影响因子：
11.1
作者：
Takaishi, K;Duplomb, L;Unger, RH
通讯作者：
Unger, RH
DOI：
10.1073/pnas.96.22.12737
发表时间：
1999-10-26
影响因子：
11.1
作者：
Foretz, M;Guichard, C;Foufelle, F
通讯作者：
Foufelle, F
影响因子：
9.8
作者：
SHRAGO, E;GLENNON, JA;GORDON, ES
通讯作者：
GORDON, ES
影响因子：
7.7
作者：
Boden, G;She, PX;Ruderman, N
通讯作者：
Ruderman, N
影响因子：
56.9
作者：
Lee, Ann-Hwee;Scapa, Erez F.;Glimcher, Laurie H.
通讯作者：
Glimcher, Laurie H.