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Diabetes 53:S66-S70, 2004
© 2004 by the American Diabetes Association, Inc.

Section II: Nuclear Receptors and Islet Function

Liver Glucokinase Can Be Activated by Peroxisome Proliferator-Activated Receptor-{gamma}

So-youn Kim1,2, Ha-il Kim1, Sang-Kyu Park1,2, Seung-Soon Im1,2, Tianzhu Li1,2, Hyae Gyeong Cheon3, and Yong-ho Ahn1,2

1 Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, Seoul, Korea
2 Brain Korea 21 Project for Medical Sciences, Yonsei University College of Medicine, Seoul, Korea
3 Pharmacology Screening Team, Korea Research Institute of Chemical Technology, Daejeon, Korea

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.

Address correspondence and reprint requests to Yong-ho Ahn, Department of Biochemistry and Molecular Biology, Center for Chronic Metabolic Disease Research, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemoon-gu, Seoul 120-752, Korea. E-mail: yha111{at}yumc.yonsei.ac.kr


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Diabetes Diabetes Care Clinical Diabetes Diabetes Spectrum
Copyright © 2004 by the American Diabetes Association.