Abramovici Y, Agarwal M K
Biochem Med. 1985 Dec;34(3):259-66. doi: 10.1016/0006-2944(85)90087-0.
A single intraperitoneal injection of 5 mg (250 mg/kg body wt) streptozotocin induced overt diabetes within 48 hr in male, 6-week-old mice of C57BL/6 and C57BL/10 (sensitive) strains. The C3H/HeJ and C3H/eb (resistant) strains exhibited a progressive delayed-onset hyperglycemia which required 6 weeks to reach the level seen within only 48 hr in sensitive strains. Resistance to SZ-induced diabetes was not related to changes in body weights or different pharmacokinetics of the drug. C3H/HeJ (resistant) mice showed a smaller fall in immunoreactive insulin pancreatic content and less severe damage of pancreatic islets on histologic examination, when compared to C57BL/6 (sensitive) mice during the first week post-SZ. These results suggest that strain-related resistance to SZ-induced diabetes may be mediated at the level of the beta cell's responsiveness to the cytotoxic action of the drug. This very simple experimental tool may be of value in monitoring the period before the onset of overt insulin-deficient diabetes and for probing the nature of factors that constitute a genetically resistant pancreas, understanding of which could aid management of diabetes mellitus in humans.
对6周龄雄性C57BL/6和C57BL/10（敏感）品系小鼠进行腹腔内单次注射5毫克（250毫克/千克体重）链脲佐菌素，48小时内会诱发明显的糖尿病。C3H/HeJ和C3H/eb（抗性）品系则表现出渐进性延迟发作的高血糖，需要6周才能达到敏感品系仅在48小时内就能达到的水平。对链脲佐菌素诱导的糖尿病的抗性与体重变化或药物不同的药代动力学无关。与链脲佐菌素注射后第一周的C57BL/6（敏感）小鼠相比，C3H/HeJ（抗性）小鼠的免疫反应性胰岛素胰腺含量下降幅度较小，组织学检查显示胰岛损伤较轻。这些结果表明，品系相关的对链脲佐菌素诱导糖尿病的抗性可能在β细胞对药物细胞毒性作用的反应水平上介导。这个非常简单的实验工具可能有助于监测明显胰岛素缺乏性糖尿病发作前的时期，并探究构成遗传抗性胰腺的因素的性质，了解这些因素有助于人类糖尿病的管理。
