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, takehiro torisu, Mako Nakaya, Takashi Kobayashi, Giichi Takaesu, Akihiko Yoshimura

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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 - Aug 10 2007

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Medical problems
Type 1 Diabetes Mellitus
Streptozocin
Cell signaling
Free Radicals
Knockout Mice
Insulin
Apoptosis
Cytokines
Experimental Diabetes Mellitus
Islets of Langerhans
DNA Damage
Inflammation

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Suppression of SOCS3 expression in the pancreatic β-cell leads to resistance to type 1 diabetes. / Mori, Hiroyuki; Shichita, Takashi; Yu, Qingsheng; Yoshida, Ryoko; Hashimoto, Masayuki; Okamoto, Fuyuki; torisu, takehiro; Nakaya, Mako; Kobayashi, Takashi; Takaesu, Giichi; Yoshimura, Akihiko.

In: Biochemical and Biophysical Research Communications, Vol. 359, No. 4, 10.08.2007, p. 952-958.

Research output: Contribution to journalArticle

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, vol. 359, no. 4, pp. 952-958. https://doi.org/10.1016/j.bbrc.2007.05.198
Mori, Hiroyuki ; Shichita, Takashi ; Yu, Qingsheng ; Yoshida, Ryoko ; Hashimoto, Masayuki ; Okamoto, Fuyuki ; torisu, takehiro ; Nakaya, Mako ; Kobayashi, Takashi ; Takaesu, Giichi ; Yoshimura, Akihiko. / Suppression of SOCS3 expression in the pancreatic β-cell leads to resistance to type 1 diabetes. In: Biochemical and Biophysical Research Communications. 2007 ; Vol. 359, No. 4. pp. 952-958.
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