Molello J A, Barnard S D, Thompson D J
Toxicol Appl Pharmacol. 1984 Feb;72(2):255-61. doi: 10.1016/0041-008x(84)90310-7.
The effects of hexamethylmelamine (HMM) on morphology and function of the endocrine pancreas were investigated following the induction of a diabetic-like syndrome in a reproduction study in rats. Doses of 0, 20, 40, or 80 mg/kg/day were administered once daily, by gavage, to groups of 10 male and 10 female Sprague-Dawley rats for up to 77 days. Signs of toxicity were observed at all treatment levels and were of such severity at 80 mg/kg/day that this group was terminated after 8 days of treatment. Measurement of serum glucose levels revealed a dose- and time-related hyperglycemia in rats from the 20- and 40-mg/kg/day groups with levels exceeding 700 mg/dl in some rats after 77 days of treatment. Reversal of the hyperglycemia after discontinuing treatment with HMM occurred in some rats receiving 20 mg/kg/day, whereas the effects of higher doses were still present following a 2-month recovery period. Microscopically, there were hydropic degeneration of renal tubular epithelium and vacuolation of pancreatic beta cells. Ultrastructurally, vesiculation of the Golgi-smooth membrane reticular complex and a marked reduction in the number of insulin granules were observed. It appeared that HMM exerted a disruptive effect on the production of insulin at or prior to the level of the Golgi complex. The severity and time course of morphologic changes and hyperglycemia were dependent on dose and duration of treatment.
在一项大鼠繁殖研究中诱发类糖尿病综合征后，研究了六甲蜜胺（HMM）对内分泌胰腺形态和功能的影响。将0、20、40或80毫克/千克/天的剂量通过灌胃每日一次给予每组10只雄性和10只雌性Sprague-Dawley大鼠，持续77天。在所有治疗水平均观察到毒性迹象，在80毫克/千克/天的剂量下毒性严重，该组在治疗8天后终止。血清葡萄糖水平测量显示，20毫克/千克/天和40毫克/千克/天组的大鼠出现剂量和时间相关的高血糖，在治疗77天后，一些大鼠的血糖水平超过700毫克/分升。在一些接受20毫克/千克/天治疗的大鼠中，停用HMM治疗后高血糖症得到逆转，而在2个月的恢复期后，高剂量的影响仍然存在。显微镜下，肾小管上皮细胞出现水样变性，胰腺β细胞出现空泡化。超微结构观察发现，高尔基体-平滑膜网状复合体出现囊泡化，胰岛素颗粒数量显著减少。看来HMM在高尔基体复合体水平或之前对胰岛素的产生产生了破坏作用。形态学变化和高血糖症的严重程度和时间进程取决于治疗剂量和持续时间。
