Cited by 145Pancreatic function and diabetesDiabetes and associated disordersNitric Oxide and Endothelin Effects

Transgenic Mice Overexpressing Type 2 Nitric-oxide Synthase in Pancreatic β Cells Develop Insulin-dependent Diabetes without Insulitis

Open access
Takamura, Toshinari, Kato, Ichiro, Kimura, Noriko, Nakazawa, Tetsuya, Yonekura, Hideto, Takasawa, Shin, Okamoto, Hiroshi·1998·Journal of Biological Chemistry

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 beta 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 beta cell NOS2 plays an essential role in the beta cell degeneration.

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Crossref · 10.1074/jbc.273.5.2493

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  • The inhibitory actions of NO on insulin release appear to be due to NOS2-derived NO, which is implicated in the destruction of islet cells in type 1 diabetes.

    “The inhibitory actions of NO on insulin release appear to be due to NOS2-derived NO, which is implicated in the destruction of islet cells in type 1 diabetes [309, 310].”

    From Regulation of obesity and insulin resistance by nitric oxide (2014) · cites this paper as [310]

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Authors
Takamura, T., Kato, I., Kimura, N., Nakazawa, T., Yonekura, H., Takasawa, S., & Okamoto, H.
Affiliations
Tohoku University (JP)
Corresponding author
Okamoto, Hiroshi
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
1998-01
Volume
273
Issue
5
Pages
2493-2496
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1972128212
Cited by
145
References
33
Citations by year
2025: 2 · 2022: 6 · 2021: 1 · 2020: 1 · 2019: 2 · 2017: 1 · 2016: 6 · 2015: 2 · 2014: 9 · 2013: 8 · 2012: 9
FWCI
12.21
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Topics
  • Health Sciences › Medicine › Surgery › Pancreatic function and diabetes
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
  • Health Sciences › Medicine › Physiology › Nitric Oxide and Endothelin Effects
Keywords
NOS2, pancreatic beta cells, beta cell degeneration, type 1 diabetes, nitric oxide, nitrite, transgenic mice, aminoguanidine, DNA strand breaks, islets, beta-cell mass, insulin promoter
MeSH terms
Animals, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 1, DNA Damage, Guanidines, Insulin, Islets of Langerhans, Mice, Transgenic, Nitrites, Organ Culture Techniques, Nitric Oxide Synthase, Mice, Nitric Oxide Synthase Type II

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