Transgenic Mice Overexpressing Type 2 Nitric-oxide Synthase in Pancreatic β Cells Develop Insulin-dependent Diabetes without Insulitis
Open accessAbstract
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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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
- hybrid
- doi.org
- Licence
- 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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