Pdx1 expression in Irs2-deficient mouse beta-cells is regulated in a strain-dependent manner - PubMed (original) (raw)

. 2003 Oct 31;278(44):43691-8.

doi: 10.1074/jbc.M307004200. Epub 2003 Jul 16.

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

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• PMID: 12869553
• DOI: 10.1074/jbc.M307004200

Free article

Pdx1 expression in Irs2-deficient mouse beta-cells is regulated in a strain-dependent manner

Ryo Suzuki et al. J Biol Chem. 2003.

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Abstract

We previously demonstrated that Irs2-/- mice develop diabetes due to beta-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 beta-cell function, was recently reported to be severely reduced in Irs2-/- murine beta-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 beta-cells with a C57BL/6 background. We have also demonstrated the expression of upstream genes of Pdx-1, such as HNF3beta and HNF1alpha, 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 beta-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 beta-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.

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