FoxO6 in glucose metabolism (FoxO6).
FoxO6 in glucose metabolism (FoxO6).
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DOI：
10.1111/1753-0407.12027
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发表时间：
2013-09
影响因子：
4.5
通讯作者：
Dong HH
中科院分区：
文献类型：
--
作者：
Kim DH;Zhang T;Lee S;Dong HH
叉头盒O亚家族有四个成员，包括FoxO1、FoxO3、FoxO4和FoxO6。与其他三个FoxO成员不同，FoxO6受到的关注要少得多，因为早期的报道称FoxO6仅限于大脑。最近的数据表明，FoxO6在啮齿动物和人类的肝脏中产生。肝脏FoxO6活性在进食状态下保持在低基础水平，在禁食小鼠中显著诱导。FoxO6活性在饮食性肥胖或2型糖尿病小鼠的肝脏中异常升高。肝脏FoxO 6活性升高的基因工程小鼠表现出糖尿病前期，最终发展为葡萄糖耐受不良、空腹高血糖和高胰岛素血症。相反，在胰岛素抵抗的肝脏中抑制FoxO6活性导致空腹高血糖症的减少，有助于改善2型糖尿病小鼠的高胰岛素血症。这些新的数据表明，FoxO6是响应胰岛素或生理线索的肝脏葡萄糖代谢的重要调节剂。胰岛素通过促进其磷酸化并使其在细胞核中的活性丧失而不改变其亚细胞分布来抑制FoxO6活性，该机制与FoxO亚家族的其他成员不同。在这篇文章中，我们将对FoxO6在健康和疾病中的葡萄糖代谢中的作用进行全面综述。我们还将讨论FoxO6失调是否是空腹高血糖症发病机制的一个促成因素，并讨论FoxO6是否是改善2型糖尿病空腹高血糖症的潜在治疗靶点。
The forkhead box O subfamily has four members including FoxO1, FoxO3, FoxO4 and FoxO6. Unlike other three FoxO members, FoxO6 has garnered considerably less attention due to earlier reports that FoxO6 is limited to the brain. Recent data indicate that FoxO6 is produced in the liver of both rodent and human origins. Hepatic FoxO6 activity, which remains at low basal levels in fed states, is markedly induced in fasted mice. FoxO6 activity becomes abnormally higher in the liver of mice with dietary obesity or type 2 diabetes. Genetically engineered mice with elevated FoxO6 activity in the liver exhibit pre-diabetes, culminating in the development of glucose intolerance, fasting hyperglycemia and hyperinsulinemia. Conversely, inhibition of FoxO6 activity in insulin-resistant liver results in the reduction of fasting hyperglycemia, contributing to the amelioration of hyperinsulinemia in type 2 diabetic mice. These new data suggest that FoxO6 is an important regulator of hepatic glucose metabolism in response to insulin or physiological cues. Insulin inhibits FoxO6 activity by promoting its phosphorylation and disabling its activity in the nucleus without altering its subcellular distribution via a mechanism that is distinct from other members of the FoxO subfamily. In this article, we will provide a comprehensive review on the role of FoxO6 in glucose metabolism in health and disease. We will also address whether FoxO6 dysregulation is a contributing factor for the pathogenesis of fasting hyperglycemia and discuss whether FoxO6 is a potential therapeutic target for improving fasting hyperglycemia in type 2 diabetes.
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影响因子：
7.8
作者：
Pawlikowska L;Hu D;Huntsman S;Sung A;Chu C;Chen J;Joyner AH;Schork NJ;Hsueh WC;Reiner AP;Psaty BM;Atzmon G;Barzilai N;Cummings SR;Browner WS;Kwok PY;Ziv E;Study of Osteoporotic Fractures
通讯作者：
Study of Osteoporotic Fractures
影响因子：
--
作者：
Cifarelli, Vincenza;Lee, Sojin;Dong, H. Henry
通讯作者：
Dong, H. Henry
FOXO6将胰岛素信号传导与肝脏中的糖异生相结合。
影响因子：
7.7
作者：
Kim DH;Perdomo G;Zhang T;Slusher S;Lee S;Phillips BE;Fan Y;Giannoukakis N;Gramignoli R;Strom S;Ringquist S;Dong HH
通讯作者：
Dong HH
影响因子：
56.9
作者：
Monecke, Thomas;Guettler, Thomas;Ficner, Ralf
通讯作者：
Ficner, Ralf
影响因子：
56.9
作者：
Lee, SS;Kennedy, S;Ruvkun, G
通讯作者：
Ruvkun, G