Wright J R, Lacy P E
Department of Pathology, Washington University School of Medicine, St. Louis, MO 63110.
Diabetes. 1988 Jan;37(1):112-8. doi: 10.2337/diab.37.1.112.
Three weekly intraperitoneal 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 greater than 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.(ABSTRACT TRUNCATED AT 250 WORDS)
据报道，每周进行三次腹腔注射完全弗氏佐剂（CFA），并在1天后注射低剂量链脲佐菌素（STZ；25mg/kg腹腔注射），可导致β细胞免疫破坏及糖尿病的逐渐发生。在本研究中，雄性Lewis大鼠腹腔注射CFA，1天后注射低剂量STZ；每周重复一次，共3周。第1、2、3和4周糖尿病（非空腹血糖大于200mg/dl）的发生率分别为50%、80%、93%和100%。仅接受CFA或STZ注射的大鼠未患糖尿病。在STZ诱导糖尿病之前，注射CFA的成分（不完全弗氏佐剂和丁酸分枝杆菌）、另一种诱导肉芽肿的微生物（单核细胞增生李斯特菌）或内毒素也可诱导糖尿病，但发病较慢，病情也比CFA和STZ诱导的糖尿病轻。由于腹腔注射CFA会引起腹腔刺激、急性体重减轻和注射后次日低血糖，我们研究了单纯禁食是否会增强低剂量STZ的作用。在低剂量STZ注射前禁食24小时和注射后禁食24小时，导致糖尿病的发病速度和严重程度与CFA和STZ诱导的相似。在STZ之前皮下注射CFA不会引起低血糖或体重减轻，但会导致糖尿病。因此，腹腔注射CFA的禁食效应并非CFA和STZ诱导糖尿病的原因。这些数据表明，免疫佐剂、内毒素和禁食均可增强低剂量STZ的致糖尿病作用。（摘要截断于250字）
