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 Citations (Scopus)

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

Fingerprint

Glucokinase
Peroxisome Proliferator-Activated Receptors
Thiazolidinediones
Liver
Response Elements
troglitazone
Retinoid X Receptors
Glucose
Glycogen
Type 2 Diabetes Mellitus
Transcriptional Activation
Hepatocytes
Homeostasis
Ligands
Messenger RNA
Mutation

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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.

Liver Glucokinase Can Be Activated by Peroxisome Proliferator-Activated Receptor-γ. / Kim, So Youn; Kim, Ha Il; Park, Sang Kyu; Im, Seung Soon; Li, Tianzhu; Cheon, Hyae Gyeong; Ahn, Yong Ho.

In: Diabetes, Vol. 53, No. SUPPL. 1, 01.02.2004, p. S66-S70.

Research output: Contribution to journalArticle

Kim, SY, Kim, HI, Park, SK, Im, SS, Li, T, Cheon, HG & Ahn, YH 2004, 'Liver Glucokinase Can Be Activated by Peroxisome Proliferator-Activated Receptor-γ', Diabetes, vol. 53, no. SUPPL. 1, pp. S66-S70.
Kim SY, Kim HI, Park SK, Im SS, Li T, Cheon HG et al. Liver Glucokinase Can Be Activated by Peroxisome Proliferator-Activated Receptor-γ. Diabetes. 2004 Feb 1;53(SUPPL. 1):S66-S70.
Kim, So Youn ; Kim, Ha Il ; Park, Sang Kyu ; Im, Seung Soon ; Li, Tianzhu ; Cheon, Hyae Gyeong ; Ahn, Yong Ho. / Liver Glucokinase Can Be Activated by Peroxisome Proliferator-Activated Receptor-γ. In: Diabetes. 2004 ; Vol. 53, No. SUPPL. 1. pp. S66-S70.
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