Gerling I, Nejman C, Chatterjee N K
Wadsworth Center for Laboratories and Research, New York State Department of Health, Albany 12201.
Diabetes. 1988 Oct;37(10):1419-25. doi: 10.2337/diab.37.10.1419.
Diabetogenic strains of Coxsackievirus B4 (CB4) produce a diabetes syndrome in susceptible mice that resembles insulin-dependent diabetes mellitus. To assess the possible role of autoimmunity, the expression of a 64,000-Mr islet antigen in SJL/J and CD1 mice infected with a diabetogenic strain of CB4 was monitored in early and late infection. Additionally, virus-induced abnormalities in glucose metabolism were correlated with several changes in purified islets to assess beta-cell physiology. Over 80% of the mice exhibited subnormal blood glucose at 72 h postinfection (p.i.) and were hyperglycemic at 6 and 8 wk p.i. Islet yield in infected mice decreased by 29-47% at 72 h and 6 wk p.i. compared to noninfected mice. Insulin release stimulated by 16.7 mM glucose increased greater than twofold at 72 h p.i. but declined at 6 wk well below the level of noninfected mice. Likewise, residual islet insulin content after release also increased at 72 h and then declined. Total protein synthesis in the islets decreased by 30% at 72 h and by 60% at 6 wk p.i. Although the synthesis of five proteins of heterogeneous molecular weights, including tubulin, was severely depressed in the infected islets at 72 h p.i. compared with control islets or islets at 6 wk p.i., synthesis of the 64,000-Mr component and another protein of 36,000 Mr increased by two- to threefold. It is possible that CB4 infection may initiate or enhance an autoimmune reaction by increased expression of the 64,000-Mr antigen.
柯萨奇病毒B4(CB4)的致糖尿病毒株可在易感小鼠中引发一种类似于胰岛素依赖型糖尿病的糖尿病综合征。为评估自身免疫可能发挥的作用,在感染早期和晚期监测了感染致糖尿病毒株CB4的SJL/J和CD1小鼠中一种64,000道尔顿胰岛抗原的表达。此外,将病毒诱导的葡萄糖代谢异常与纯化胰岛中的若干变化相关联,以评估β细胞生理功能。超过80%的小鼠在感染后72小时(p.i.)血糖低于正常水平,而在感染后6周和8周出现高血糖。与未感染小鼠相比,感染小鼠在感染后72小时和6周时胰岛产量下降了29 - 47%。16.7 mM葡萄糖刺激的胰岛素释放在感染后72小时增加了两倍多,但在6周时下降,远低于未感染小鼠的水平。同样,释放后残留的胰岛胰岛素含量在72小时也增加,然后下降。胰岛中的总蛋白质合成在感染后72小时下降了30%,在感染后6周下降了60%。尽管与对照胰岛或感染后6周的胰岛相比,感染后72小时感染胰岛中包括微管蛋白在内的五种分子量各异的蛋白质合成严重受抑,但64,000道尔顿成分和另一种36,000道尔顿蛋白质的合成增加了两到三倍。CB4感染有可能通过增加64,000道尔顿抗原的表达引发或增强自身免疫反应。