Leiter E H
Proc Natl Acad Sci U S A. 1982 Jan;79(2):630-4. doi: 10.1073/pnas.79.2.630.
Insulin-dependent diabetes induced in susceptible strains of mice by multiple, low-dose streptozotocin treatment has been proposed to entail a thymus-dependent, autoimmune destruction of beta cells. In this study, thymectomized and genetically athymic mice have been tested for susceptibility to streptozotocin. Thymectomy was performed on newborn (day 1) to 3-day-old C57BL/KsJ mice. At 8 wk of age, thymectomized and sham-operated mice of both sexes were tested for susceptibility to diabetes induction by multiple, low-dose streptozotocin treatment (35 mg/kg of body weight per day for 6 consecutive days). Thymectomy failed to block susceptibility of males to induction of severe hyperglycemia. Beta cell necrosis and inflammatory cell infiltrates (insulitis) were consistent histopathological features. In general, females-both thymus-intact and thymectomized-were less susceptible than males to streptozotocin-induced hyperglycemia, and females exhibited an equally severe insulitis by experimental day 14; thus, the detection of an underlying insulitis did not predict the development of a more severe hyperglycemia because most streptozotocin-treated females at experimental day 35 continued to show only a modest hyperglycemia (about 200 mg/dl) compared to males (>400 mg/dl). That streptozotocin-induced hyperglycemia could occur in the absence of an intact thymus was further demonstrated in genetically athymic C57BL/6J NIcrOu nu/nu males and thymus-intact +/? littermate controls. C57BL/6J mice were resistant to streptozotocin-induced insulitis. This study shows that the presence of insulitis does not necessarily presage onset of severe hyperglycemia (e.g., C57BL/KsJ females), and conversely, the presence of severe hyperglycemia after low-dose streptozotocin treatment is not necessarily diagnostic of an underlying insulitis (e.g., C57BL/6J +/? and nu/nu males). These data stress the need for caution in the interpretation of studies of streptozotocin-insulitis sensitivities of nude mice.
多次低剂量链脲佐菌素处理诱导易感品系小鼠发生胰岛素依赖型糖尿病，这一过程被认为涉及胸腺依赖性的β细胞自身免疫性破坏。在本研究中，对胸腺切除的和基因缺陷无胸腺的小鼠进行了链脲佐菌素易感性测试。对新生（第1天）至3日龄的C57BL/KsJ小鼠实施胸腺切除术。8周龄时，对胸腺切除和假手术的雌雄小鼠进行多次低剂量链脲佐菌素处理（每天35mg/kg体重，连续6天）以测试糖尿病诱导易感性。胸腺切除术未能阻止雄性小鼠对严重高血糖诱导的易感性。β细胞坏死和炎性细胞浸润（胰岛炎）是一致的组织病理学特征。一般而言，胸腺完整和胸腺切除的雌性小鼠比雄性小鼠对链脲佐菌素诱导的高血糖更不易感，并且到实验第14天雌性小鼠表现出同样严重的胰岛炎；因此，检测到潜在的胰岛炎并不能预测更严重高血糖的发展，因为与雄性小鼠（>400mg/dl）相比，大多数链脲佐菌素处理的雌性小鼠在实验第35天仅持续表现出适度的高血糖（约200mg/dl）。基因缺陷无胸腺的C57BL/6J NIcrOu nu/nu雄性小鼠和胸腺完整的+/?同窝对照进一步证明，在没有完整胸腺的情况下也可发生链脲佐菌素诱导的高血糖。C57BL/6J小鼠对链脲佐菌素诱导的胰岛炎具有抗性。本研究表明，胰岛炎的存在不一定预示着严重高血糖的发生（例如C57BL/KsJ雌性小鼠），相反，低剂量链脲佐菌素处理后严重高血糖的存在不一定诊断为潜在的胰岛炎（例如C57BL/6J +/?和nu/nu雄性小鼠）。这些数据强调在解释裸鼠链脲佐菌素-胰岛炎敏感性研究时需要谨慎。
