Karam J H, Lewitt P A, Young C W, Nowlain R E, Frankel B J, Fujiya H, Freedman Z R, Grodsky G M
Diabetes. 1980 Dec;29(12):971-8. doi: 10.2337/diab.29.12.971.
A clinical syndrome, characterized by acute diabetic ketoacidosis associated with a toxic neuropathy, developed in five men who intentionally ingested a recently introduced rodenticide (Vacor) containing N-3-pyridylmethyl-N'-p-nitrophenyl urea (RH-787). A 7-yr-old boy, who accidentally ingested this poison, died within 14 h. Marked insulinopenia, without a reduction in glucagon levels, suggested a specific beta-cytotoxic effect, which was supported after autopsy in three cases by histopathologic evidence of extensive beta cell destruction. Lethal effects in rats prevented investigation of RH-787's diabetogenicity in vivo; however, studies in isolated rat islets confirmed a direct inhibitory effect, which was prevented by concomitant incubation with nicotinamide, suggesting a mechanism of action similar to that of streptozotocin. We detected islet cell-surface antibodies in two of four patients studied. These findings indicate that this nongenetic, acquired form of insulinopenic diabetes, which has persisted in the surviving patients for up to 3 yr, presents a unique opportunity to test in man the concept that hyperglycemia and the accompanying metabolic consequences of insulinopenia can induced diabetic microangiopathy in the absence of genetic predisposition.
五名男性故意摄入了一种新推出的含有N-3-吡啶甲基-N'-对硝基苯基脲（RH-787）的灭鼠剂（Vacor）后，出现了一种临床综合征，其特征为急性糖尿病酮症酸中毒伴有中毒性神经病变。一名7岁男孩意外摄入这种毒物后，在14小时内死亡。显著的胰岛素缺乏，而胰高血糖素水平未降低，提示存在一种特异性的β细胞毒性作用，三例尸检的组织病理学证据显示广泛的β细胞破坏，支持了这一观点。大鼠的致死效应妨碍了对RH-787体内致糖尿病性的研究；然而，对分离的大鼠胰岛的研究证实了其直接抑制作用，同时与烟酰胺孵育可防止这种作用，提示其作用机制与链脲佐菌素相似。在研究的四名患者中有两名检测到胰岛细胞表面抗体。这些发现表明，这种非遗传性、获得性胰岛素缺乏型糖尿病在存活患者中持续长达3年，为在人体中检验高血糖和胰岛素缺乏伴随的代谢后果可在无遗传易感性的情况下诱发糖尿病微血管病变这一概念提供了独特的机会。
