Zeng Chunhua, Hou Guoqing, Dick Robert, Brewer George J
University of Michigan Medical School, 5024 Kresge Bldg. II, Ann Arbor, MI 48109-0534, USA.
Exp Biol Med (Maywood). 2008 Aug;233(8):1021-5. doi: 10.3181/0801-RM-10. Epub 2008 May 14.
The objective was to evaluate whether copper lowering therapy with tetrathiomolybdate (TM) affected blood sugar levels in three rodent models of diabetes, streptozotocin (STZ) treated rats and mice, and the db/db mouse model. STZ was administered to rats and mice, and blood sugar levels were followed over a protracted time in these and non-STZ control animals. TM was administered by oral gavage (rats) or in the drinking water (mice) to a portion of the rats and mice to observe effects on blood sugar. Mice with genetically determined diabetes (db/db) were studied by giving half the mice TM in the drinking water and following blood sugar. The results show that TM caused a significant reduction in blood glucose in both STZ treated rats and mice, but no effect on blood glucose in db/db mice. However, TM caused a significant reduction in proteinuria in db/db animals. The results are discussed around the likelihood that TM is inhibiting ongoing inflammatory damage in the pancreas from STZ. A metabolic effect of TM on blood glucose is possible but seems less likely. TM is also likely inhibiting inflammatory and/or fibrogenic effects in the kidneys of db/db mice.
目的是评估用四硫代钼酸盐(TM)进行的降铜疗法是否会影响三种糖尿病啮齿动物模型(链脲佐菌素(STZ)处理的大鼠和小鼠以及db/db小鼠模型)的血糖水平。给大鼠和小鼠注射STZ,并在较长时间内跟踪这些动物和非STZ对照动物的血糖水平。通过口服灌胃(大鼠)或饮水(小鼠)的方式给一部分大鼠和小鼠施用TM,以观察对血糖的影响。通过给一半饮用含TM水的小鼠喂食并跟踪血糖,对具有遗传性糖尿病的小鼠(db/db)进行研究。结果表明,TM使STZ处理的大鼠和小鼠的血糖显著降低,但对db/db小鼠的血糖没有影响。然而,TM使db/db动物的蛋白尿显著减少。围绕TM抑制STZ对胰腺持续炎症损伤的可能性对结果进行了讨论。TM对血糖可能有代谢作用,但可能性较小。TM也可能抑制db/db小鼠肾脏中的炎症和/或纤维化作用。