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Seo, Young Kyo
School of Life Sciences
Research Interests
  • How the fundamental processes of gene regulation are used in the control and management of metabolic homeostasis

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Regulation of IGFBP-2 expression during fasting

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Title
Regulation of IGFBP-2 expression during fasting
Author
Kang, Hye SukKim, Mi-YoungKim, Seung-JaeLee, Jae-HoKim, Yong-DeukSeo, Young KyoBae, Jae-HoonOh, Goo-TaegSong, Dae-KyuAhn, Yong-HoIm, Seung-Soon
Issue Date
2015-05
Publisher
PORTLAND PRESS LTD
Citation
BIOCHEMICAL JOURNAL, v.467, pp.453 - 460
Abstract
Insulin-like growth factor (IGF)-binding protein-2 (IGFBP-2), one of the most abundant circulating IGFBPs, is known to attenuate the biological action of IGF-1. Although the effect of IGFBP-2 in preventing metabolic disorders is well known, its regulatory mechanism remains unclear. In the present study, we demonstrated the transcriptional regulation of the Igfbp-2 gene by peroxisome-proliferator-activated receptor (PPAR) alpha in the liver. During fasting, both Igfbp-2 and PPAR alpha expression levels were increased. Wy14643, a selective PPAR alpha agonist, significantly induced Igfbp-2 gene expression in primary cultured hepatocytes. However, Igfbp-2 gene expression in Ppar alpha null mice was not affected by fasting or Wy14643. In addition, through transient transfection and chromatin immunoprecipitation assay in fasted livers, we determined that PPAR alpha bound to the putative PPAR-responsive element between -511 bp and -499 bp on the Igfbp-2 gene promoter, indicating that the Igfbp-2 gene transcription is activated directly by PPAR alpha. To explore the role of PPAR alpha in IGF-1 signalling, we treated primary cultured hepatocytes with Wy14643 and observed a decrease in the number of IGF-1 receptors (IGF-1Rs) and in Akt phosphorylation. No inhibition was observed in the hepatocytes isolated from Ppar alpha null mice. These results suggest that PPAR alpha controls IGF-1 signalling through the up-regulation of hepatic Igfbp-2 transcription during fasting and Wy14643 treatment
URI
https://scholarworks.unist.ac.kr/handle/201301/17182
URL
http://www.biochemj.org/content/467/3/453
DOI
10.1042/BJ20141248
ISSN
0264-6021
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