SYNERGISTIC EFFECTS OF ADJUVANTS, ENDOTOXIN, AND FASTING ON INDUCTION OF DIABETES WITH MULTIPLE LOW-DOSES OF STREPTOZOCIN IN RATS
SYNERGISTIC EFFECTS OF ADJUVANTS, ENDOTOXIN, AND FASTING ON INDUCTION OF DIABETES WITH MULTIPLE LOW-DOSES OF STREPTOZOCIN IN RATS
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DOI：
10.2337/diabetes.37.1.112
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发表时间：
1988-01-01
期刊：
影响因子：
7.7
通讯作者：
LACY, PE
中科院分区：
文献类型：
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作者：
WRIGHT, JR;LACY, PE
每周三次腹腔注射完全弗氏S佐剂，1天后，小剂量链脲佐菌素(STZ；25 mg/kg，i.p)。已被报道会导致β细胞的免疫破坏和糖尿病的逐渐发病。在这项研究中，雄性Lewis大鼠被注射CFA，并在1天后注射小剂量STZ；每周重复一次，持续3wk。糖尿病(非空腹血糖200 mg/dl)在第1、2、3、4周的发生率分别为50%、80%、93%和100%。只接受CFA或STZ治疗的大鼠没有发生糖尿病。在STZ诱导糖尿病前注射CFA成分(不完全弗氏佐剂和酪酸分枝杆菌)、另一种肉芽肿诱生微生物(单核细胞增生性李斯特菌)或内毒素，但起病慢，糖尿病严重程度轻于CFA和STZ。由于腹腔注射CFA会在注射后第二天引起腹膜刺激、急性体重减轻和低血糖，我们检查了禁食是否单独加强了小剂量的STZ。小剂量STZ前、后禁食24小时可致糖尿病，其发病速度和严重程度与CFA和STZ相似。STZ前皮下注射CFA不会导致低血糖或体重减轻，但确实会导致糖尿病。因此，腹膜腔内CFA的禁食效应并不是CFA和STZ诱发糖尿病的原因。这些数据表明，免疫佐剂、内毒素和禁食都加强了小剂量STZ的促糖尿病作用。在单次注射CFA和小剂量STZ后48小时内，大鼠糖尿病发病率为50%，这表明在该模型中，免疫系统不参与糖尿病的调节。此外，用CFA和低剂量STZ造成糖尿病的8只大鼠，胰岛同种异体移植没有排斥反应。
Three weekly intraperitonel injections of complete Freund''s adjuvant (CFA) and, 1 day later, low-dose streptozocin (STZ; 25 mg/kg i.p.) have been reported to cause immune destruction of .beta.-cells and a gradual onset of diabetes mellitus. In this study, male Lewis rats were injected intraperitoneally with CFA and 1 day later with low-dose STZ; these were repeated at weekly intervals for 3 wk. The incidence of diabetes mellitus (nonfasted plasma glucose > 200 mg/dl) in wk 1, 2, 3, and 4 was 50, 80, 93, and 100%, respectively. Rats receiving either CFA or STZ only did not develop diabetes. Injections of either the components of CFA (incomplete Freund''s adjuvant and Mycobacterium butyricum), another granuloma-inducing organism (Listeria monocytogenes), or endotoxin before STZ induced diabetes, but the onset was slower and the diabetes was less severe than with CFA and STZ. Because intraperitoneal CFA injections caused peritoneal irritation, acute weight loss, and hypoglycemia on the day after injection, we examined whether fasting alone potentiated low-dose STZ. Fasting for 24 h before and 24 h after low-dose STZ caused diabetes that was similar in rapidity of onset and severity to that induced with CFA and STZ. Administration of CFA subcutaneously before STZ did not cause hypoglycemia or weight loss but did cause diabetes. Thus, the fasting effect of intraperitoneal CFA was not responsible for the induction of diabetes with CFA and STZ. These data indicate that immunologic adjuvants, endotoxin, and fasting all potentiate the diabetogenic action of low-dose STZ. The 50% incidence of diabetes in rats within 48 h of a single injection of CFA and low-dose STZ suggests that the immune system does not mediate diabetes in this model. Furthermore, transplants of islet isografts were not rejected by eight rats made diabetic with CFA and low-dose STZ.