Liver Glucokinase Can Be Activated by Peroxisome Proliferator-Activated Receptor-γ

So Youn Kim, Ha Il Kim, Sang Kyu Park, Seung Soon Im, Tianzhu Li, Hyae Gyeong Cheon, Yong Ho Ahn

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Thiazolidinediones (TZDs), synthetic ligands of peroxisome proliferator-activated receptor (PPAR)-γ, 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-γ/retinoid X receptor-α 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-γ. Furthermore, troglitazone increased endogenous GK mRNA in primary hepatocytes. These results indicate that PPAR-γ can directly activate GK expression in liver and may contribute to improving glucose homeostasis in type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)S66-S70
JournalDiabetes
Volume53
Issue numberSUPPL. 1
StatePublished - Feb 1 2004

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Kim, S. Y., Kim, H. I., Park, S. K., Im, S. S., Li, T., Cheon, H. G., & Ahn, Y. H. (2004). Liver Glucokinase Can Be Activated by Peroxisome Proliferator-Activated Receptor-γ. Diabetes, 53(SUPPL. 1), S66-S70.