NITRIC-OXIDE PRODUCTION IN ISLETS FROM NONOBESE DIABETIC MICE - AMINOGUANIDINE-SENSITIVE AND AMINOGUANIDINE-RESISTANT STAGES IN THE IMMUNOLOGICAL DIABETIC PROCESS
NITRIC-OXIDE PRODUCTION IN ISLETS FROM NONOBESE DIABETIC MICE - AMINOGUANIDINE-SENSITIVE AND AMINOGUANIDINE-RESISTANT STAGES IN THE IMMUNOLOGICAL DIABETIC PROCESS
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DOI：
10.1073/pnas.90.19.8992
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发表时间：
1993-10-01
影响因子：
11.1
通讯作者：
UNANUE, ER
中科院分区：
文献类型：
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作者：
CORBETT, JA;MIKHAEL, A;UNANUE, ER
一氧化氮的作用(No.)在免疫诱导糖尿病的发展过程中进行了检查。将从糖尿病雌性非肥胖糖尿病(NOD)小鼠获得的脾细胞移植到非糖尿病照射的雄性小鼠，在移植后11-13天诱发糖尿病。从受体雄性小鼠分离的胰岛产生NO。以一种时间依赖的方式。移植后第6天开始检测到亚硝酸盐的产生，第9天和第13天增加。在相似条件下，在脾细胞移植后第6天、第9天和第13天，葡萄糖诱导的NOD小鼠胰岛胰岛素分泌不可逆转地减少约40%。移植后第9天和第13天每个胰腺收获的胰岛数量比对照组减少了20-25%。用NO诱导型抑制剂氨基胍治疗雄性NOD小鼠。合成酶，减少了NO的产生。并使糖尿病的发展延迟3-8天。氨基胍对小鼠脾细胞的暂时抑制作用依赖于抑制物浓度和脾细胞转移量。这些结果表明，没有。作为免疫糖尿病过程的结果，该化合物在NOD胰岛中产生，提示该化合物在免疫性糖尿病过程中的作用。
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 almost-equal-to 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.