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

The Journal of Biological Chemistry
T TakamuraH Okamoto

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.

References

May 5, 1978·Science·V B ReddyS M Weissman
Sep 22, 1989·Cell·P N EpsteinA R Means
Mar 16, 1983·Biochemical and Biophysical Research Communications·K Nose, H Okamoto
Oct 1, 1982·Analytical Biochemistry·L C GreenS R Tannenbaum
Aug 1, 1995·American Journal of Respiratory Cell and Molecular Biology·K J PendinoD L Laskin
Mar 30, 1994·Biochemical and Biophysical Research Communications·J RadonsH Kolb

❮ Previous
Next ❯

Citations

Aug 10, 2000·Diabetes/metabolism Research and Reviews·H E Thomas, T W Kay
Jun 30, 2000·Biochemical and Biophysical Research Communications·T TabatabaieY Kotake
Oct 18, 2000·Biochemical and Biophysical Research Communications·A SjöholmR V Cooney
Feb 25, 2010·Pflügers Archiv : European journal of physiology·Hiroaki Shimokawa, Masato Tsutsui
Dec 13, 2012·Current Hypertension Reports·Robrecht ThoonenEmmanuel S Buys
Jul 22, 1999·Diabetes Research and Clinical Practice·T TakamuraK Kobayashi
Oct 5, 2001·Trends in Genetics : TIG·M Gannon
Feb 1, 2000·Trends in Endocrinology and Metabolism : TEM·T W KayJ Allison
Dec 15, 2010·The British Journal of Nutrition·Zhuo FuDongmin Liu
Oct 19, 1999·The Journal of Experimental Medicine·S T GreyC Ferran
Mar 28, 2012·Journal of Diabetes Investigation·Yasuhiko Yamamoto, Hiroshi Yamamoto
Jun 17, 2004·Molecular and Cellular Biology·Matthew G HartmanTsonwin Hai
May 12, 2009·Circulation Journal : Official Journal of the Japanese Circulation Society·Masato TsutsuiNobuyuki Yanagihara
Jan 6, 2007·International Journal of Biological Sciences·Natalia MakeevaNils Welsh
Jun 19, 2013·Journal of UOEH·Kiyoko ShibataMasato Tsutsui
Feb 22, 2001·Biochemical and Biophysical Research Communications·A K AnderssonS Sandler
Nov 17, 2007·Proceedings of the National Academy of Sciences of the United States of America·Yalin EmreDaniel Ricquier
Aug 26, 2014·Inflammopharmacology·Manpreet KaurPuneet Kumar
Jul 17, 2007·Biochemical and Biophysical Research Communications·Hiroshi KanamoriHidenori Arai
Jan 18, 2013·Annals of the New York Academy of Sciences·Lindsey E PadgettHubert M Tse
Jul 18, 2001·The Journal of Clinical Investigation·Y YamamotoH Yamamoto
Jul 20, 2012·Epigenetics : Official Journal of the DNA Methylation Society·Elizabeth R Gilbert, Dongmin Liu
Jun 1, 2014·Free Radical Biology & Medicine·Brian E Sansbury, Bradford G Hill

❮ Previous
Next ❯

Related Concepts

Related Feeds

ASBMB Publications

The American Society for Biochemistry and Molecular Biology (ASBMB) includes the Journal of Biological Chemistry, Molecular & Cellular Proteomics, and the Journal of Lipid Research. Discover the latest research from ASBMB here.

Autoimmune Diabetes & Tolerance

Patients with type I diabetes lack insulin-producing beta cells due to the loss of immunological tolerance and autoimmune disease. Discover the latest research on targeting tolerance to prevent diabetes.