CRTC2 (TORC2) contributes to the transcriptional response to fasting in the liver but is not required for the maintenance of glucose homeostasis.
CRTC2 (TORC2) contributes to the transcriptional response to fasting in the liver but is not required for the maintenance of glucose homeostasis.
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DOI：
10.1016/j.cmet.2009.06.006
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发表时间：
2009-07
期刊：
影响因子：
29
通讯作者：
Kaestner KH
中科院分区：
文献类型：
--
作者：
Le Lay J;Tuteja G;White P;Dhir R;Ahima R;Kaestner KH
肝脏通过促进葡萄糖的储存或产生（取决于生理状态）来促进葡萄糖稳态。cAMP反应元件结合蛋白（CREB）是参与协调肝脏对禁食反应的基因的主要调节因子，但其基因激活机制仍存在争议。我们衍生CRTC 2-（CREB调节的转录辅激活因子2;以前TORC 2）缺陷小鼠，以评估这种辅因子对体内肝脏葡萄糖代谢的贡献。CRTC 2突变肝细胞显示对胰高血糖素的葡萄糖产生减少，这与CREB与几种致炎基因结合减少相关。然而，尽管CREB靶基因（包括PEPCK、G6 β和PGC 1 α）的表达减弱，但在突变小鼠中未观察到低血糖。总的来说，这些结果提供了支持CRTC 2在对禁食的转录反应中的作用的遗传证据，但表明该辅因子对维持葡萄糖稳态的贡献有限。
The liver contributes to glucose homeostasis by promoting either storage or production of glucose depending on the physiological state. The cAMP response element binding protein (CREB) is a principal regulator of genes involved in coordinating the hepatic response to fasting, but its mechanism of gene activation remains controversial. We derived CRTC2-(CREB-regulated transcription coactivator 2; previously TORC2) deficient mice to assess the contribution of this cofactor to hepatic glucose metabolism in vivo. CRTC2 mutant hepatocytes showed reduced glucose production in response to glucagon, which correlated with decreased CREB binding to several gluconeogenic genes. However, despite attenuated expression of CREB target genes including PEPCK, G6Pase, and PGC1α, no hypoglycemia was observed in mutant mice. Collectively, these results provide genetic evidence supporting a role for CRTC2 in the transcriptional response to fasting, but indicate only a limited contribution of this cofactor to the maintenance of glucose homeostasis.
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影响因子：
11.4
作者：
Xu, Wu;Kasper, Lawryn H.;Brindle, Paul K.
通讯作者：
Brindle, Paul K.
影响因子：
64.8
作者：
Alenghat, Theresa;Meyers, Katherine;Mullican, Shannon E.;Leitner, Kirstin;Adeniji-Adele, Adetoun;Avila, Jacqueline;Bucan, Maja;Ahima, Rexford S.;Kaestner, Klaus H.;Lazar, Mitchell A.
通讯作者：
Lazar, Mitchell A.
影响因子：
64.8
作者：
Liu, Yi;Dentin, Renaud;Chen, Danica;Hedrick, Susan;Ravnskjaer, Kim;Schenk, Simon;Milne, Jill;Meyers, David J.;Cole, Phil;Yates, John, III;Olefsky, Jerrold;Guarente, Leonard;Montminy, Marc
通讯作者：
Montminy, Marc
DOI：
10.1073/pnas.1932773100
发表时间：
2003-10-14
影响因子：
11.1
作者：
Iourgenko, V;Zhang, WJ;Labow, MA
通讯作者：
Labow, MA
影响因子：
5.3
作者：
She, P;Shiota, H;Magnuson, MA
通讯作者：
Magnuson, MA