Pdx1 Expression in Irs2-deficient Mouse β-Cells Is Regulated in a Strain-dependent Manner

Ryo Suzuki, Kazuyuki Tobe, Yasuo Terauchi, Kajuro Komeda, Naoto Kubota, Kazuhiro Eto, Toshimasa Yamauchi, Kousuke Azuma, Hideaki Kaneto, Takashi Taguchi, Teiichiro Koga, Michael S. German, Hirotaka Watada, Ryuzo Kawamori, Christopher V.E. Wright, Yoshitaka Kajimoto, Satoshi Kimura, Ryozo Nagai, Takashi Kadowaki*

*この論文の責任著者

研究成果: ジャーナルへの寄稿学術論文査読

31 被引用数 (Scopus)

抄録

We previously demonstrated that Irs2-/- mice develop diabetes due to β-cell growth failure and insulin resistance; however, glucose-induced insulin secretion was increased in islets isolated from Irs2-/- mice. Pdx-1, a transcription factor important for maintenance of the β-cell function, was recently reported to be severely reduced in Irs2-/- murine β-cells. We report herein that Pdx-1 expression, including the amount of Pdx-1 localized in the nucleus, is not down-regulated in our Irs2-/- murine β-cells with a C57BL/6 background. We have also demonstrated the expression of upstream genes of Pdx-1, such as HNF3β and HNF1α, as well as its downstream genes, including insulin, Glut2, and Nkx6.1, to be well preserved. We have further demonstrated Pdx-1 expression to also be preserved in β-cells of 30-week-old diabetic Irs2-/- mice. In addition, surprisingly, even in Irs2-/- mice on a high fat diet with markedly elevated blood glucose, exceeding 400 mg/dl, Pdx-1 expression was not reduced. Furthermore, we found Pdx-1 to be markedly decreased in certain severely diabetic Irs2-/- mice with a mixed C57BL/6J x 129Sv background. We conclude that 1) Pdx-1 expression in Irs2-/- mice is regulated in a strain-dependent manner, 2) Irs2 -/- mice develop diabetes associated with β-cell growth failure even when Pdx1 expression is preserved, and 3) Pdx-1 expression is preserved in severely hyperglycemic Irs2-/- mice with a C57BL/6 background on a high fat diet.

本文言語英語
ページ(範囲)43691-43698
ページ数8
ジャーナルJournal of Biological Chemistry
278
44
DOI
出版ステータス出版済み - 2003/10/31

ASJC Scopus 主題領域

  • 生化学
  • 分子生物学
  • 細胞生物学

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