Role of Krüppel-like factor 15 in PEPCK gene expression in the liver.
Regulation of hepatic gene expression is important for energy homeostasis. We now show that hepatic expression of the gene for the transcription factor Kruppel-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.
Teshigawara
Kiyoshi
K
Department of Clinical Molecular Medicine, Division of Diabetes and Digestive and Kidney Diseases, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan.
Ogawa
Wataru
W
Mori
Toshiyuki
T
Matsuki
Yasushi
Y
Watanabe
Eijiro
E
Hiramatsu
Ryuji
R
Inoue
Hiroshi
H
Miyake
Kazuaki
K
Sakaue
Hiroshi
H
Kasuga
Masato
M
D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000031:analogs & derivatives / Q000494:pharmacology; D004268:DNA-Binding Proteins; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation; D004591:Electrophoresis, Polyacrylamide Gel; D015971:Gene Expression Regulation, Enzymologic; D015309:Glucose Clamp Technique / Q000379:methods; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology; D051741:Kruppel-Like Transcription Factors; D008099:Liver / Q000378:metabolism*; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010729:Phosphoenolpyruvate Carboxykinase (GTP) / Q000235:genetics / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D051381:Rats; D014157:Transcription Factors / Q000737:chemistry / Q000502:physiology*
D000242:Cyclic AMP; D004268:DNA-Binding Proteins; D003907:Dexamethasone; D007328:Insulin; D051741:Kruppel-Like Transcription Factors; D019869:Phosphatidylinositol 3-Kinases; D010729:Phosphoenolpyruvate Carboxykinase (GTP); D000081082:Phosphoinositide-3 Kinase Inhibitors; D014157:Transcription Factors; C467418:Klf15 protein, mouse