Ishimura E, Nishizawa Y, Koyama H, Shoji S, Inaba M, Morii H
Second Department of Internal Medicine, Osaka City University Medical School, Japan.
Miner Electrolyte Metab. 1995;21(1-3):205-10.
Several studies of diabetes mellitus patients have demonstrated abnormalities in calcium, phosphate and vitamin D metabolism. In an earlier study, the authors reported impaired renal processing of phosphate in spontaneously diabetic GK rats, an animal model of type II diabetes mellitus. In the present study, which represents an extension of the earlier study, vitamin D metabolism and response are examined in 20-week-old GK rats. Serum 1,25-dihydroxyvitamin D [1,25-(OH)2D] was found to be lower in GK rats than in Wistar rats. After intraperitoneal administration of 0.5 micrograms/kg 1,25-(OH)2D, serum calcium increased in GK rats, but not in Wistar rats, while serum phosphate remained unchanged in GK rats, but increased in Wistar rats. Although serum 1,25-(OH)2D rose abruptly in 3 h and decreased thereafter in both GK and Wistar rats, the decrease in serum 1,25-(OH)2D at 6 h was more marked in GK rats than in Wistar rats. Serum 24,25-dihydroxyvitamin D was consistently higher in GK rats than in Wistar rats. Northern blotting and dot blotting with use of a cDNA probe for the 24-hydroxylase gene showed an increased expression of the gene in the kidney of GK rats. These results demonstrate impaired vitamin D metabolism in GK rats. Increased activity of 24-hydroxylase, in addition to impaired phosphate metabolism, may play a role in impaired vitamin D metabolism in GK rats.
多项针对糖尿病患者的研究表明，其钙、磷及维生素D代谢存在异常。在一项早期研究中，作者报告了自发性糖尿病GK大鼠（II型糖尿病动物模型）的肾脏对磷的处理功能受损。在本研究中，作为早期研究的延伸，对20周龄的GK大鼠的维生素D代谢及反应进行了检测。结果发现，GK大鼠的血清1,25 - 二羟维生素D [1,25-(OH)₂D] 低于Wistar大鼠。腹腔注射0.5微克/千克的1,25-(OH)₂D后，GK大鼠的血清钙升高，而Wistar大鼠未升高；GK大鼠的血清磷保持不变，而Wistar大鼠的血清磷升高。尽管在GK大鼠和Wistar大鼠中，血清1,25-(OH)₂D在3小时时均突然升高，随后下降，但在6小时时，GK大鼠血清1,25-(OH)₂D的下降比Wistar大鼠更明显。GK大鼠的血清24,25 - 二羟维生素D始终高于Wistar大鼠。使用24 - 羟化酶基因的cDNA探针进行Northern印迹和斑点印迹分析显示，GK大鼠肾脏中该基因的表达增加。这些结果表明GK大鼠存在维生素D代谢受损的情况。除了磷代谢受损外，24 - 羟化酶活性增加可能在GK大鼠维生素D代谢受损中起作用。
