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Hepatic Lipid Molecules Synergize with Insulin to Induce GK Gene Expression
Author(s) -
Gao Yifei,
Lu Danhong,
Newgard Christopher B,
Chen Guoxun
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1089.4
Subject(s) - glucokinase , insulin , endocrinology , medicine , gene expression , hepatocyte , chemistry , messenger rna , hexokinase , biology , gene , biochemistry , metabolism , in vitro , glycolysis
Hepatic glucokinase (GK, Hexokinase IV) plays a key role in maintaining glucose homoestasis. A variety of hormonal and nutritional stimuli, including insulin, regulate its activity by controlling its gene transcription. Here, we report a simple method to extract lipid molecules from rat livers and measure their effects on GK gene expression in primary rat hepatocytes using real‐time polymerase chain reaction. To this end, we observed that a lipid extract (LE) prepared rat liver by saponification, induces the levels of GK transcripts and potentates insulin‐mediated induction of GK gene expression. In hepatocytes, LE or 1 nM insulin alone induced GK mRNA by 7.6 ± 5.9‐ and 19.3 ± 12.4 –fold, respectively. The combination of LE and 1 nM insulin induced the GK expression by 155 ± 72 –fold, much higher than the sum of the induction fold by them individually (7.6+19.3=26.9), suggesting a synergy between LE and insulin. The synergy exists for all of the insulin concentrations examined ranging from 0.1 to 100 nM. LE does not induce the levels of GK transcripts in pancreatic islets and INS‐1 insulinoma cells, demonstrating a specific effect on hepatic GK expression. The actions of LE start as early as 3 hours and last at least 12 hours. Moreover, it does not alter the stability of GK transcripts, suggesting a transcriptional mechanism. We conclude that endogenous lipid molecules from liver can modulate hepatocyte GK gene expression.