Islet mass plays a critical role in initiation, but not progression, of the diabetogenic process in NOD mice.
Islet mass plays a critical role in initiation, but not progression, of the diabetogenic process in NOD mice.
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胰岛质量在 NOD 小鼠糖尿病发生过程的起始而非进展中发挥着关键作用。
DOI：
10.1006/jaut.1999.0283
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发表时间：
1999
期刊：
影响因子：
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通讯作者：
Maki,T
中科院分区：
文献类型：
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作者：
Kimura,T;Ito,A;Hancock,WW;Maki,T
Pancreatectomy (90%) at a preinsulitis age (7 weeks) protects NOD mice from diabetes while pancreatectomy at a mid-insulitis age (13 weeks) has no such protective effect. The present study examined the effects of islet transplantation in pancreatectomized diabetes-free NOD mice. Transplantation of syngeneic NOD islets as well as allogeneic C3H/He and C57BL/6 islets 3 weeks after pancreatectomy-induced spontaneous diabetes whereas transplantation of xenogeneic Sprague–Dawley rat islets or allogeneic C3H/He skin failed to induce diabetes, demonstrating that the diabetogenic antigen(s) of NOD islets is also expressed by islets of diabetes-resistant mouse strains but not by xenogeneic rat islets. Removal of NOD islet grafts by nephrectomy 7–14 days after transplantation had no effect on the subsequent chronic development of diabetes, while graft removal 3 days after transplantation completely abolished the diabetogenic effect of islet transplantation. Thus, activation of the diabetogenic response by islet isografting takes less than 7 days and the continuous presence of a large islet mass is not required for progression to diabetes. While islet transplantation at 10 and 15 weeks of age caused diabetes, delayed islet transplantation at 23 and 35 weeks of age failed to induce diabetes in pancreatectomized diabetes-free NOD mice, suggesting that initiation of the diabetogenic autoimmune process must take place within a certain window of time. The pancreatectomy/islet transplantation model is excellent for studying the immunological events surrounding activation and progression of the diabetogenic autoimmune process and for identifying the diabetogenic islet antigen(s).
