Role of Krüppel-like factor 15 in PEPCK gene expression in the liver

Kiyoshi Teshigawara, Wataru Ogawa, Toshiyuki Mori, Yasushi Matsuki, Eijiro Watanabe, Ryuji Hiramatsu, Hiroshi Inoue, Kazuaki Miyake, Hiroshi Sakaue, Masato Kasuga

Research output: Contribution to journalArticlepeer-review

46 Citations (Scopus)

Abstract

Regulation of hepatic gene expression is important for energy homeostasis. We now show that hepatic expression of the gene for the transcription factor Krüppel-like factor 15 (KLF15) is increased by food deprivation and reduced by feeding in mice. Expression of the KLF15 gene in mouse liver was also down-regulated by a euglycemic-hyperinsulinemic clamp and was increased by inhibition of phosphatidylinositol 3-kinase. In cultured rat hepatocytes, KLF15 gene expression was induced by dexamethasone and a non-hydrolyzing analog of cAMP, and this effect was inhibited by insulin in a manner dependent on phosphatidylinositol 3-kinase signaling. Forced expression of KLF15 in cultured hepatocytes increased both the expression and the promoter activity of the gene for phosphoenolpyruvate carboxykinase (PEPCK). These results suggest that insulin and its counteracting hormones regulate the hepatic expression of KLF15, and that this transcription factor contributes to the regulation of PEPCK gene expression in the liver.

Original languageEnglish
Pages (from-to)920-926
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume327
Issue number3
DOIs
Publication statusPublished - Feb 18 2005

Keywords

  • Gene expression
  • Insulin action
  • KLF15
  • Liver
  • PI 3-kinase

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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