Transgenic mice overexpressing type 2 nitric-oxide synthase in pancreatic β cells develop insulin-dependent diabetes without insulitis

Toshinari Takamura, Ichiro Kato, Noriko Kimura, Tetsuya Nakazawa, Hideto Yonekura, Shin Takasawa, Hiroshi Okamoto

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123 Citations (Scopus)

Abstract

We generated transgenic mice carrying the mouse type 2 nitric-oxide synthase (NOS2) cDNA under the control of the insulin promoter. Western and immunohistochemical analyses revealed that NOS2 was expressed abundantly in transgenic islets but not in control islets. When islets were isolated and cultured, high levels of nitrite were released from the transgenic islets. In transgenic mice, the β cell mass was markedly reduced without the infiltration of macrophages or lymphocytes, and extensive DNA strand breaks were detected in the islets by in situ nick translation. All the transgenic mice developed hypoinsulinemic diabetes by 4 weeks of age, and treatment with an inhibitor of NOS2, aminoguanidine (200 mg/kg body weight every 12 h), prevented or delayed the development of diabetes. The present study shows that the production of nitric oxide by β cell NOS2 plays an essential role in the β cell degeneration.

Original languageEnglish
Pages (from-to)2493-2496
Number of pages4
JournalJournal of Biological Chemistry
Volume273
Issue number5
DOIs
Publication statusPublished - 1998 Jan 30

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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