Effects of Dehydroepiandrosterone on Gluconeogenic Enzymes and Glucose Uptake in Human Hepatoma Cell Line, HepG2

  • YAMASHITA Ryo
    Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine Department of Metabolic Disorder, Research Institute, International Medical Center of Japan
  • SAITO Tatsuya
    Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine
  • SATOH Shinobu
    Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine
  • AOKI Kazutaka
    Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine
  • KABURAGI Yasushi
    Department of Metabolic Disorder, Research Institute, International Medical Center of Japan
  • SEKIHARA Hisahiko
    Department of Endocrinology and Metabolism, Yokohama City University Graduate School of Medicine Japan Labour Health and Welfare Organization

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抄録

Dehydroepiandrosterone (DHEA), the most abundant human adrenal steroid, improves insulin sensitivity and obesity in human and model animals. In a previous study, we reported that orally administered DHEA suppresses the elevated activities of hepatic gluconeogenic enzymes like glucose-6-phosphatase (G6Pase) in C57BL/KsJ-db/db mice (Aoki K, Saito T, Satoh S, Mukasa K, Kaneshiro M, Kawasaki S, Okamura A, Sekihara H (1999) Diabetes 48: 1579–1585). However, the molecular mechanisms by which DHEA ameliorates insulin resistance are not clearly understood. In the present study, we cultured the human hepatoma cell line HepG2 with DHEA and measured the enzyme activity and protein expression of G6Pase to investigate the direct effect of DHEA on glucose metabolism in hepatocytes. DHEA significantly suppressed both the activity and protein expression of G6Pase. Moreover, DHEA decreased the gene expression of G6Pase and phosphoenolpyruvate carboxykinase, both of which were maximal at 1 μM DHEA, whereas the mRNA level of glucose-6-phosphate translocase was unchanged. Furthermore, DHEA enhanced 2-deoxyglucose uptake, although its effect was much smaller than that of insulin. These results suggest that DHEA may act at multiple steps in the regulation of glucose metabolism in the liver.<br>

収録刊行物

  • Endocrine Journal

    Endocrine Journal 52 (6), 727-733, 2005

    一般社団法人 日本内分泌学会

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