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Regulation of IGFBP-2 expression during fasting

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Affiliated Author(s)
이재호배재훈송대규임승순
Alternative Author(s)
Lee, Jae HoBae, Jae HoonSong, Dae KyuIm, Seung Soon
Journal Title
Biochemical Journal
ISSN
0264-6021
Issued Date
2015
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) α in
the liver. During fasting, both Igfbp-2 and PPARα expression
levels were increased. Wy14643, a selective PPARα agonist,
significantly induced Igfbp-2 gene expression in primary cultured
hepatocytes. However, Igfbp-2 gene expression in Pparα null
micewas not affected by fasting orWy14643. In addition, through
transient transfection and chromatin immunoprecipitation assay
in fasted livers, we determined that PPARα 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 PPARα. To explore the
role of PPARα 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
Pparα null mice. These results suggest that PPARα controls
IGF-1 signalling through the up-regulation of hepatic Igfbp-2
transcription during fasting and Wy14643 treatment.
Key words: fasting, gene expression, insulin-like growth factor-1
(IGF-1), insulin-like growth factor-binding protein 2 (IGFBP-2),
liver, peroxisome-proliferator-activated receptor α (PPARα).
Department
Dept. of Anatomy (해부학)
Dept. of Physiology (생리학)
Publisher
School of Medicine
Citation
Hye Suk Kang et al. (2015). Regulation of IGFBP-2 expression during fasting. Biochemical Journal, 467(3), 453–460. doi: 10.1042/BJ20141248
Type
Article
ISSN
0264-6021
DOI
10.1042/BJ20141248
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/35183
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Anatomy (해부학)
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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