学術雑誌論文

学術雑誌論文

Cell Reports. 2014, 7(6), p. 1876-1886

NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling

Elsevier B.V.

英語

2014-06-26

https://doi.org/10.1016/j.celrep.2014.05.030

Beiying Qiu, Xiaohe Shi, Ee Tsin Wong, Joy Lim, Marco Bezzi, Diana Low, Qiling Zhou, Semih Can Akıncılar, Manikandan Lakshmanan, Hannah L.F. Swa, Jill Mae Lan Tham, Jayantha Gunaratne, Kenneth K.Y. Cheng, Wanjin Hong, Karen S.L. Lam, Masahito Ikawa, Ernesto Guccione, Aimin Xu, Weiping Han, Vinay Tergaonkar, NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling, Cell Reports, Volume 7, Issue 6, 2014, Pages 1876-1886, ISSN 2211-1247, https://doi.org/10.1016/j.celrep.2014.05.030.

Although much is known about the molecular players in insulin signaling, there is scant information about transcriptional regulation of its key components. We now find that NUCKS is a transcriptional regulator of the insulin signaling components, including the insulin receptor (IR). Knockdown of NUCKS leads to impaired insulin signaling in endocrine cells. NUCKS knockout mice exhibit decreased insulin signaling and increased body weight/fat mass along with impaired glucose tolerance and reduced insulin sensitivity, all of which are further exacerbated by a high-fat diet (HFD). Genome-wide ChIP-seq identifies metabolism and insulin signaling as NUCKS targets. Importantly, NUCKS is downregulated in individuals with a high body mass index and in HFD-fed mice, and conversely, its levels increase upon starvation. Altogether, NUCKS is a physiological regulator of energy homeostasis and glucose metabolism that works by regulating chromatin accessibility and RNA polymerase II recruitment to the promoters of IR and other insulin pathway modulators.

© 2014 The Authors. Published by Elsevier Inc. This article is licensed under a Creative Commons Attribution 3.0 Unported License.

78601

NUCKS Is a Positive Transcriptional Regulator of Insulin Signaling

Elsevier B.V.

英語

2014-06-26

Cell Reports

7

6

1876

1886

https://doi.org/10.1016/j.celrep.2014.05.030

24931609

https://hdl.handle.net/11094/78601