title: Regulation of IGFBP-2 expression during fasting.
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 mice was not affected by fasting or Wy14643. 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.
authors.affiliation: *Department of Physiology, Keimyung University School of Medicine, Daegu 704-701, Republic of Korea.
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Kang
authors.affiliation: †Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Kim
authors.affiliation: *Department of Physiology, Keimyung University School of Medicine, Daegu 704-701, Republic of Korea.
authors.forename: Seung-Jae
authors.initials: SJ
authors.lastname: Kim
authors.affiliation: *Department of Physiology, Keimyung University School of Medicine, Daegu 704-701, Republic of Korea.
authors.forename: Jae-Ho
authors.initials: JH
authors.lastname: Lee
authors.affiliation: *Department of Physiology, Keimyung University School of Medicine, Daegu 704-701, Republic of Korea.
authors.forename: Yong-Deuk
authors.initials: YD
authors.lastname: Kim
authors.affiliation: ‡School of Life Sciences, UNIST, Ulsan 689-798, Republic of Korea.
authors.forename: Young-Kyo
authors.initials: YK
authors.lastname: Seo
authors.affiliation: *Department of Physiology, Keimyung University School of Medicine, Daegu 704-701, Republic of Korea.
authors.forename: Jae-Hoon
authors.initials: JH
authors.lastname: Bae
authors.affiliation: §Division of Life and Pharmaceutical Sciences, Ewha Womans University, Seoul 120-750, Republic of Korea.
authors.forename: Goo-Taeg
authors.initials: GT
authors.lastname: Oh
authors.affiliation: *Department of Physiology, Keimyung University School of Medicine, Daegu 704-701, Republic of Korea.
authors.forename: Dae-Kyu
authors.initials: DK
authors.lastname: Song
authors.affiliation: †Department of Biochemistry and Molecular Biology, Yonsei University College of Medicine, Seoul 120-752, Republic of Korea.
authors.forename: Yong-Ho
authors.initials: YH
authors.lastname: Ahn
authors.affiliation: *Department of Physiology, Keimyung University School of Medicine, Daegu 704-701, Republic of Korea.
authors.forename: Seung-Soon
authors.initials: SS
authors.lastname: Im
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005215:Fasting / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D047493:PPAR alpha / Q000172:deficiency / Q000235:genetics; D047495:PPAR gamma / Q000819:agonists; D020025:Peroxisome Proliferators / Q000494:pharmacology; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077154:Rosiglitazone; D015398:Signal Transduction; D045162:Thiazolidinediones / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D018971:Insulin-Like Growth Factor Binding Protein 2; D047493:PPAR alpha; D047495:PPAR gamma; D020025:Peroxisome Proliferators; D011743:Pyrimidines; D012333:RNA, Messenger; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D007334:Insulin-Like Growth Factor I; C006253:pirinixic acid; D051057:Proto-Oncogene Proteins c-akt