Metformin-induced suppression of glucose-6-phosphatase expression is independent of insulin signaling in rat hepatoma cells

  • Authors:
    • Kohei Morioka
    • Kaname Nakatani
    • Kazutaka Matsumoto
    • Hideki Urakawa
    • Nagako Kitagawa
    • Akira Katsuki
    • Yasuko Hori
    • Esteban C. Gabazza
    • Yutaka Yano
    • Junji Nishioka
    • Tsutomu Nobori
    • Yasuhiro Sumida
    • Yukihiko Adachi
  • View Affiliations

  • Published online on: March 1, 2005     https://doi.org/10.3892/ijmm.15.3.449
  • Pages: 449-452
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Abstract

Metformin is thought to decrease blood glucose levels by reducing hepatic glucose output. To elucidate the pharmacological action of metformin on hepatic glucose production, we examined its effect on the gene expression of glucose-6-phosphatase (G6Pase), a key enzyme of gluconeogenesis, in H4IIE rat hepatoma cell line by RT-PCR and quantitative real-time PCR. Metformin suppressed dexamethasone/cAMP-induced expression of G6Pase mRNA in a dose dependent manner, its maximum effect being observed at 2 mM (79.3% inhibition, P<0.05). Pretreatment with the PI3-kinase inhibitor wortmannin, the MEK-1 inhibitor PD98059 or the protein kinase C inhibitor GF109203X had no effect on suppressed G6Pase expression by metformin. Moreover, metformin did not stimulate Akt phosphorylation. In the present study, we demonstrate that metformin suppresses G6Pase mRNA expression by a mechanism that is independent of the activation of PI3-kinase, Akt, MAP kinase and protein kinase C pathway in hepatocytes.

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March 2005
Volume 15 Issue 3

Print ISSN: 1107-3756
Online ISSN:1791-244X

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Spandidos Publications style
Morioka K, Nakatani K, Matsumoto K, Urakawa H, Kitagawa N, Katsuki A, Hori Y, Gabazza EC, Yano Y, Nishioka J, Nishioka J, et al: Metformin-induced suppression of glucose-6-phosphatase expression is independent of insulin signaling in rat hepatoma cells. Int J Mol Med 15: 449-452, 2005.
APA
Morioka, K., Nakatani, K., Matsumoto, K., Urakawa, H., Kitagawa, N., Katsuki, A. ... Adachi, Y. (2005). Metformin-induced suppression of glucose-6-phosphatase expression is independent of insulin signaling in rat hepatoma cells. International Journal of Molecular Medicine, 15, 449-452. https://doi.org/10.3892/ijmm.15.3.449
MLA
Morioka, K., Nakatani, K., Matsumoto, K., Urakawa, H., Kitagawa, N., Katsuki, A., Hori, Y., Gabazza, E. C., Yano, Y., Nishioka, J., Nobori, T., Sumida, Y., Adachi, Y."Metformin-induced suppression of glucose-6-phosphatase expression is independent of insulin signaling in rat hepatoma cells". International Journal of Molecular Medicine 15.3 (2005): 449-452.
Chicago
Morioka, K., Nakatani, K., Matsumoto, K., Urakawa, H., Kitagawa, N., Katsuki, A., Hori, Y., Gabazza, E. C., Yano, Y., Nishioka, J., Nobori, T., Sumida, Y., Adachi, Y."Metformin-induced suppression of glucose-6-phosphatase expression is independent of insulin signaling in rat hepatoma cells". International Journal of Molecular Medicine 15, no. 3 (2005): 449-452. https://doi.org/10.3892/ijmm.15.3.449