Nitric oxide production in islets from nonobese diabetic mice: aminoguanidine-sensitive and -resistant stages in the immunological diabetic process. Proc Natl Acad Sci U S A 1993 Oct 01;90(19):8992-5
Date
10/01/1993Pubmed ID
7692442Pubmed Central ID
PMC47487DOI
10.1073/pnas.90.19.8992Scopus ID
2-s2.0-0027489210 (requires institutional sign-in at Scopus site) 154 CitationsAbstract
The role of nitric oxide (NO.) in the development of immunologically induced diabetes was examined. Transfer of spleen cells obtained from diabetic female nonobese diabetic (NOD) mice to nondiabetic irradiated males induced diabetes 11-13 days after transfer. Islets isolated from recipient male mice produced NO. in a time-dependent fashion. The production of nitrite was initially detected at day 6 after transfer, with increasing levels by days 9 and 13. Under similar conditions glucose-induced insulin secretion by isolated NOD mouse islets was irreversibly reduced by approximately 40% at days 6, 9, and 13 after transfer of spleen cells. The number of islets harvested per pancreas by the 9th and 13th day after transfer was decreased by 20-25% as compared to controls. Treatment of male NOD mice with aminoguanidine, an inhibitor of the inducible form of NO. synthase, reduced the production of NO. in islets and delayed the development of diabetes by 3-8 days. The temporary inhibition by aminoguanidine was dependent on both inhibitor concentration and number of spleen cells transferred. These results indicate that NO. is produced in NOD islets as a result of an immunological diabetogenic process and suggests a role of this compound in the immunological diabetic process.
Author List
Corbett JA, Mikhael A, Shimizu J, Frederick K, Misko TP, McDaniel ML, Kanagawa O, Unanue ERAuthor
John A. Corbett PhD Chair, Professor in the Biochemistry department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Amino Acid OxidoreductasesAnimals
Diabetes Mellitus, Type 1
Female
Guanidines
Immunotherapy, Adoptive
Islets of Langerhans
Lymphocytes
Male
Mice
Mice, Inbred NOD
Nitric Oxide
Nitric Oxide Synthase
Spleen
