Nitric oxide production in islets from nonobese diabetic mice: Aminoguanidine-sensitive and -resistant stages in the immunological diabetic process

John A. Corbett, Anwar Mikhael, Jun Shimizu, Katherine Frederick, Thomas P. Misko, Michael L. Mcdaniel, Osami Kanagawa, Emil R. Unanue

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Abstract

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 ≈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.

Original languageEnglish
Pages (from-to)8992-8995
Number of pages4
JournalProceedings of the National Academy of Sciences of the United States of America
Volume90
Issue number19
DOIs
StatePublished - Oct 1 1993

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