MULTIPLE LOW-DOSE STREPTOZOTOCIN-INDUCED HYPERGLYCEMIA AND INSULITIS IN C57BL-MICE - INFLUENCE OF INBRED BACKGROUND, SEX, AND THYMUS
MULTIPLE LOW-DOSE STREPTOZOTOCIN-INDUCED HYPERGLYCEMIA AND INSULITIS IN C57BL-MICE - INFLUENCE OF INBRED BACKGROUND, SEX, AND THYMUS
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DOI：
10.1073/pnas.79.2.630
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发表时间：
1982-01-01
期刊：
影响因子：
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通讯作者：
LEITER, EH
中科院分区：
文献类型：
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作者：
LEITER, EH
经多次低剂量链脲佐菌素治疗，小鼠易感品系可诱导胰岛素依赖型糖尿病，引起胸腺依赖性的自身免疫破坏。细胞。研究了去胸腺小鼠和遗传性胸腺缺失小鼠对链脲佐菌素的敏感性。对新生（第1天）至3日龄C57BL/KsJ小鼠进行胸腺切除术。8周龄时，对去胸腺和假手术小鼠进行多次低剂量链脲佐菌素治疗（每天35 mg/kg体重，连续6天），检测小鼠对糖尿病诱导的易感性。胸腺切除术未能阻断男性对诱导严重高血糖的易感性。细胞坏死和炎症细胞浸润（胰岛素炎）是一致的组织病理学特征。总的来说，雌性（完整胸腺和切除胸腺）对链脲霉素引起的高血糖的易感性低于雄性，雌性在实验第14天表现出同样严重的胰岛素炎；因此，检测到潜在的胰岛素炎并不能预测更严重的高血糖的发展，因为大多数接受链脲佐菌素治疗的女性在实验第35天仍然只表现出中度高血糖。200毫克/分升)，而男性为400毫克/分升。在基因胸腺发育不全的C57BL/6J NIcrOu /nu男性和胸腺完整的+/？同窝出生仔畜控制。C57BL/6J小鼠对链脲佐菌素诱导的胰岛素有抵抗性。胰岛素的存在并不一定预示着严重高血糖的发生（例如，C57BL/Ks女性），相反，低剂量链脲霉素治疗后出现严重高血糖并不一定是潜在胰岛素的诊断(例如，C57BL/6J +/？和nu/nu男性)。这些数据强调在解释裸鼠链脲佐菌素-胰岛素敏感性的研究时需要谨慎。
Insulin-dependent diabetes induced in susceptible strains of mice by multiple, low-dose streptozotocin treatment was proposed to entail a thymus-dependent, autoimmune destruction of .beta. cells. Thymectomized and genetically athymic mice were 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 wt 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 (.apprx. 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. The presence of insulitis does not necessarily presage onset of severe hyperglycemia (e.g., C57BL/Ks 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.