Yonh-Ho Ahn

Publications (2)9.55 Total impact

• Article: PPARα upregulates hepatic glucose-6-phosphatase expression in fasting and DB/DB diabetic mice

  Seung-Soon Im, Mi-Young Kim, Sool-Ki Kwon, Tae-Hyun Kim, Jin-Sik Bae, Hail Kim, Kyung-Sup Kim, Goo-Taeg Oh, Yonh-Ho Ahn
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  ABSTRACT: Glucose-6-phosphatase (G6Pase) is a key liver enzyme in glucose synthesis activated by hyperglycemic conditions caused by fasting or type 2 diabetes mellitus (T2DM). These conditions activate the peroxisome proliferator activated receptor alpha (PPARα), which is thought to contribute to increased hepatic glucose output via unknown mechanisms involving G6Pase. We found that hepatic G6Pase and phosphoenolpyruvate carboxykinase (PEPCK) levels did not increase in fasting PPARα null mice, suggesting that PPARα is required for G6Pase expression. Consistent with this model, treatment of primary-cultured hepatocytes with the PPAR agonist Wy14,643 increased G6Pase mRNA levels. In addition, we identified and characterized a PPARα responsive element (PPRE) in the promoter region of the G6Pase gene. Chromatin immunoprecipitation (ChIP) assays demonstrated that the levels of PPARα/RXRα bound to the PPRE of the G6Pase promoter were higher in fasting wild type mice and db/db mice than in wild type fed control mice. These results indicate that PPARα stimulates glucose production by upregulating hepatic G6Pase gene expression caused by fasting or type 2 diabetes in mice.
  Journal of Biological Chemistry 11/2010; · 4.77 Impact Factor
• Article: Peroxisome proliferator-activated receptor {alpha} is responsible for the up-regulation of hepatic glucose-6-phosphatase gene expression in fasting and db/db Mice.

  Seung-Soon Im, Mi-Young Kim, Sool-Ki Kwon, Tae-Hyun Kim, Jin-Sik Bae, Hail Kim, Kyung-Sup Kim, Goo-Taeg Oh, Yong-Ho Ahn
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  ABSTRACT: Glucose-6-phosphatase (G6Pase) is a key enzyme that is responsible for the production of glucose in the liver during fasting or in type 2 diabetes mellitus (T2DM). During fasting or in T2DM, peroxisome proliferator-activated receptor α (PPARα) is activated, which may contribute to increased hepatic glucose output. However, the mechanism by which PPARα up-regulates hepatic G6Pase gene expression in these states is not well understood. We evaluated the mechanism by which PPARα up-regulates hepatic G6Pase gene expression in fasting and T2DM states. In PPARα-null mice, both hepatic G6Pase and phosphoenolpyruvate carboxykinase levels were not increased in the fasting state. Moreover, treatment of primary cultured hepatocytes with Wy14,643 or fenofibrate increased the G6Pase mRNA level. In addition, we have localized and characterized a PPAR-responsive element in the promoter region of the G6Pase gene. Chromatin immunoprecipitation (ChIP) assay revealed that PPARα binding to the putative PPAR-responsive element of the G6Pase promoter was increased in fasted wild-type mice and db/db mice. These results indicate that PPARα is responsible for glucose production through the up-regulation of hepatic G6Pase gene expression during fasting or T2DM animal models.
  Journal of Biological Chemistry 11/2010; 286(2):1157-64. · 4.77 Impact Factor