Suppression of SOCS3 expression in the pancreatic β-cell leads to resistance to type 1 diabetes

Hiroyuki Mori, Takashi Shichita, Qingsheng Yu, Ryoko Yoshida, Masayuki Hashimoto, Fuyuki Okamoto, Takahiro Torisu, Mako Nakaya, Takashi Kobayashi, Giichi Takaesu, Akihiko Yoshimura

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16 Citations (Scopus)

Abstract

Type 1 diabetes results from the selective destruction of insulin-producing pancreatic β-cells during islet inflammation, which involves inflammatory cytokines and free radicals. However, mechanisms for protecting β-cells from destruction have not been clarified. In this study, we define the role of SOCS3 on β-cell destruction using β-cell-specific SOCS3-conditional knockout (cKO) mice. The β-cell-specific SOCS3-deficient mice were resistant to the development of diabetes caused by streptozotocin (STZ), a genotoxic methylating agent, which has been used to trigger β-cell destruction. The islets from cKO mice demonstrated hyperactivation of STAT3 and higher induction of Bcl-xL than did islets from WT mice, and SOCS3-deficient β-cells were more resistant to apoptosis induced by STZ in vitro than were WT β-cells. These results suggest that enhanced STAT3 signaling protects β-cells from destruction induced by a genotoxic stress and that STAT3/SOCS3 can be a potential therapeutic target for the treatment of type 1 diabetes.

Original languageEnglish
Pages (from-to)952-958
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume359
Issue number4
DOIs
Publication statusPublished - 2007 Aug 10

Keywords

  • Beta-cell
  • Diabetes
  • Inflammatory cytokine
  • SOCS
  • STAT
  • Streptozotocin

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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  • Cite this

    Mori, H., Shichita, T., Yu, Q., Yoshida, R., Hashimoto, M., Okamoto, F., Torisu, T., Nakaya, M., Kobayashi, T., Takaesu, G., & Yoshimura, A. (2007). Suppression of SOCS3 expression in the pancreatic β-cell leads to resistance to type 1 diabetes. Biochemical and Biophysical Research Communications, 359(4), 952-958. https://doi.org/10.1016/j.bbrc.2007.05.198