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J Biol Chem, Vol. 273, Issue 5, 2493-2496, January 30, 1998
Cells Develop Insulin-dependent Diabetes
without Insulitis
,,,,, and
From the 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 Department of Biochemistry and the
¶ Department of Pathology, Tohoku University School of Medicine,
Sendai 980-77, Miyagi, Japan
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 cell NOS2 plays an essential role in the cell
degeneration.
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