Schneider L E, Omdahl J, Schedl H P
Endocrinology. 1976 Sep;99(3):793-9. doi: 10.1210/endo-99-3-793.
We studied diabetic rats, 5 days after streptozotocin injection, and matched controls to determine whether depressed duodenal calcium absorption associated with uncontrolled diabetes in the rat would respond to vitamin D or its metabolites. At the appropriate time following the intravenous injection of 0.25 mug of either vitamin D3, 25-hydroxycholecalciferol (25-OHD3), 1,25-dihydroxycholecalciferol (1,25-OH)2D3), or 1alpha-hydroxycholecalciferol (1alpha-OHD3) to half of each diabetic and control group, calcium transport was evaluated using everted duodenal sacs with 0.4 mM40Ca and tracer 45Ca on both mucosal and serosal surfaces. All agents stimulated duodenal calcium absorption in controls. Diabetics responded only to 1,25-(OH)2D3, the metabolite that acts directly on the duodenum, and to its synthetic analog, 1alpha-OHD3. 1alpha-OHD3 is activated to 1,25-(OH)2D3 by 25-hydroxylation in the liver; 25-OHD3 must be 1alpha-hydroxylated in the kidney to be active. The stimulation of duodenal calcium absorption in diabetic rats by 1alpha-OHD3, but not by either vitamin D3 or 25-OHD3, is most consistent with a defect in vitamin D metabolism at the 1alpha-hydroxylation step in the kidney.
我们研究了链脲佐菌素注射5天后的糖尿病大鼠及其配对对照，以确定大鼠中与未控制的糖尿病相关的十二指肠钙吸收降低是否会对维生素D或其代谢产物产生反应。在向每组糖尿病和对照组的一半静脉注射0.25微克维生素D3、25-羟基胆钙化醇（25-OHD3）、1,25-二羟基胆钙化醇（1,25-(OH)2D3）或1α-羟基胆钙化醇（1α-OHD3）后的适当时间，使用外翻十二指肠囊，在黏膜和浆膜表面分别加入0.4 mM的40Ca和示踪剂45Ca来评估钙转运。所有试剂都刺激了对照组的十二指肠钙吸收。糖尿病大鼠仅对直接作用于十二指肠的代谢产物1,25-(OH)2D3及其合成类似物1α-OHD3有反应。1α-OHD3在肝脏中通过25-羟化作用被激活为1,25-(OH)2D3；25-OHD3必须在肾脏中进行1α-羟化才能发挥活性。1α-OHD3而非维生素D3或25-OHD3对糖尿病大鼠十二指肠钙吸收的刺激作用，最符合肾脏中1α-羟化步骤的维生素D代谢缺陷。
