The role of FOXO in the regulation of metabolism
The role of FOXO in the regulation of metabolism
复制标题
DOI：
10.1007/s11892-009-0034-5
复制
发表时间：
2009-06-01
影响因子：
4.2
通讯作者：
Birnbaum, Morris J.
中科院分区：
文献类型：
--
作者：
Gross, Danielle N.;Wan, Min;Birnbaum, Morris J.
Forkhead box O(FOXO)转录因子在调节代谢功能中起着重要作用。FOXO受到几种修饰的调节，但最关键的是Akt的磷酸化和核排斥。鉴于胰岛素信号对Akt介导的FOXO磷酸化的影响，以及Foxo1在胰岛素反应组织中的相对高表达，该转录因子高度有望调节能量代谢。当营养和胰岛素水平较低时，Foxo1会促进糖异生酶的表达。相反，在进食状态下，胰岛素水平上升，并刺激葡萄糖主要被骨骼肌和包括脂肪组织在内的其他器官吸收。在某些病理生理条件下，包括胰岛素抵抗，对Foxo1的负面信号会受到影响。进一步阐明Foxo1在胰岛素反应组织中的作用将加深我们的理解，使我们能够更好地抗击胰岛素抵抗和糖尿病。
Forkhead box O (FOXO) transcription factors play an important role in modulating metabolic functions. FOXO is regulated by several modifications, but one of the most critical is phosphorylation and nuclear exclusion by Akt. Given the impact of insulin signaling on Akt-mediated phosphorylation of FOXO and the relatively high expression of Foxo1 in insulin-responsive tissues, this transcription factor is highly poised to regulate energy metabolism. When nutrient and insulin levels are low, Foxo1 promotes expression of gluconeogenic enzymes. Conversely, in the fed state, insulin levels rise and stimulate uptake of glucose primarily into skeletal muscle and other organs, including adipose tissue. Under certain pathophysiologic conditions, including insulin resistance, negative signaling to Foxo1 is compromised. Further clarification of the role of Foxo1 in insulinresponsive tissues will strengthen our understanding and allow us to better combat insulin resistance and diabetes mellitus.