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Liver glucokinase can be activated by peroxisome proliferator-activated receptor-gamma

 So-Youn Kim  ;  Ha-Il Kim  ;  Sang-Kyu Park  ;  Seung-Soon Im  ;  Tianzhu Li  ;  Hyae Gyeong Cheon  ;  Yong-Ho Ahn 
 DIABETES, Vol.53(1) : S66-S70, 2004-02 
Journal Title
Issue Date
Animals ; Cell Line ; Chromans / pharmacology ; Diabetes Mellitus, Type 2 / genetics ; Diabetes Mellitus, Type 2 / metabolism ; Dimerization ; Enzyme Activation ; Gene Expression Regulation, Enzymologic / drug effects ; Glucokinase / genetics ; Glucokinase / metabolism* ; Glucose / metabolism ; Hypoglycemic Agents / pharmacology ; Liver / metabolism* ; Protein Biosynthesis ; Rats ; Receptors, Cytoplasmic and Nuclear / drug effects ; Receptors, Cytoplasmic and Nuclear / metabolism ; Receptors, Cytoplasmic and Nuclear / physiology* ; Receptors, Retinoic Acid / genetics ; Receptors, Retinoic Acid / metabolism ; Recombinant Proteins / metabolism ; Retinoic Acid Receptor alpha ; Thiazolidinediones / pharmacology ; Transcription Factors / drug effects ; Transcription Factors / metabolism ; Transcription Factors / physiology* ; Transcription, Genetic ; Transfection ; Troglitazone
Thiazolidinediones (TZDs), synthetic ligands of peroxisome proliferator-activated receptor (PPAR)-gamma, are known to decrease hepatic glucose production and increase glycogen synthesis in diabetic animals. Recently it was reported that glucokinase (GK) expression was increased by TZDs in the liver of diabetic ZDF rats. However, the mechanism whereby TZDs increase GK expression is not yet studied. We have assumed that liver type glucokinase (LGK) induction by TZDs could be achieved by direct transcriptional activation. Thus, we have dissected the LGK promoter to explore the presence of a PPAR response element (PPRE) in the promoter. From this study, we were able to localize a PPRE in the -116/-104 region of the rat LGK gene. The PPAR-gamma/retinoid X receptor-alpha heterodimer was bound to the element and activated the LGK promoter. The LGK promoter lacking the PPRE or having mutations in the PPRE could not be activated by PPAR-gamma. Furthermore, troglitazone increased endogenous GK mRNA in primary hepatocytes. These results indicate that PPAR-gamma can directly activate GK expression in liver and may contribute to improving glucose homeostasis in type 2 diabetes.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Kim, Ha Il(김하일)
Ahn, Yong Ho(안용호) ORCID logo https://orcid.org/0000-0002-4133-0757
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