NITRIC-OXIDE PRODUCTION IN ISLETS FROM NONOBESE DIABETIC MICE - AMINOGUANIDINE-SENSITIVE AND AMINOGUANIDINE-RESISTANT STAGES IN THE IMMUNOLOGICAL DIABETIC PROCESS

The role of nitric oxide (NO.) in the development of immunologically i nduced diabetes was examined. Transfer of spleen cells obtained from d iabetic 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 pro duction of nitrite was initially detected at day 6 after transfer, wit h increasing levels by days 9 and 13. Under similar conditions glucose -induced insulin secretion by isolated NOD mouse islets was irreversib ly reduced by almost-equal-to 40% at days 6, 9, and 13 after transfer of spleen cells. The number of islets harvested per pancreas by the 9t h and 13th day after transfer was decreased by 20-25% as compared to c ontrols. Treatment of male NOD mice with aminoguanidine, an inhibitor of the inducible form of NO. synthase, reduced the production of NO. i n islets and delayed the development of diabetes by 3-8 days. The temp orary inhibition by aminoguanidine was dependent on both inhibitor con centration and number of spleen cells transferred. These results indic ate that NO. is produced in NOD islets as a result of an immunological diabetogenic process and suggests a role of this compound in the immu nological diabetic process.