Wilson G L, Gaines K L
Toxicol Appl Pharmacol. 1983 May;68(3):375-9. doi: 10.1016/0041-008x(83)90281-8.
Human ingestion of the rodenticide Vacor has been implicated in the onset of diabetes mellitus. We report here studies of the effects of Vacor on cultured rat pancreatic beta cells and fibroblasts to determine if this agent preferentially intoxicates insulin-producing beta cells. Cytotoxicity in beta cells was monitored both by phase contrast microscopy and the release of insulin into the culture medium. Changes in cellular protein were correlated with morphologic observations to determine fibroblast viability. Beta cells were 10-fold more sensitive to the toxic effects of Vacor than were fibroblasts. Vacor toxicity was reduced by treatment with nicotinamide but was unchanged by 3-O-methyl glucose. Both of these agents reduced the toxic effects of the known beta cell poison streptozotocin. The present studies indicate that Vacor possesses a toxic affinity for pancreatic beta cells and that its mechanism of toxicity may be similar but not identical to that of streptozotocin.
人类摄入灭鼠药 Vacor 与糖尿病的发病有关。我们在此报告关于 Vacor 对培养的大鼠胰腺β细胞和成纤维细胞影响的研究，以确定该药剂是否优先毒害产生胰岛素的β细胞。通过相差显微镜和胰岛素释放到培养基中的情况监测β细胞的细胞毒性。细胞蛋白质的变化与形态学观察相关联，以确定成纤维细胞的活力。β细胞对 Vacor 毒性作用的敏感性比成纤维细胞高 10 倍。用烟酰胺处理可降低 Vacor 的毒性，但 3 - O - 甲基葡萄糖对其无影响。这两种药剂都降低了已知的β细胞毒物链脲佐菌素的毒性作用。目前的研究表明，Vacor 对胰腺β细胞具有毒性亲和力，其毒性机制可能与链脲佐菌素相似但不完全相同。
