Effects of vitamin D and its metabolites on calcium transport in the diabetic rat.
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.
D000818:Animals; D001835:Body Weight; D002118:Calcium / Q000378:metabolism*; D002762:Cholecalciferol / Q000494:pharmacology*; D003920:Diabetes Mellitus / Q000139:chemically induced / Q000378:metabolism*; D004100:Dihydroxycholecalciferols / Q000494:pharmacology*; D004386:Duodenum / Q000187:drug effects / Q000378:metabolism*; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006887:Hydroxycholecalciferols / Q000494:pharmacology*; D007408:Intestinal Absorption / Q000187:drug effects*; D008297:Male; D051381:Rats; D013311:Streptozocin
D004100:Dihydroxycholecalciferols; D006887:Hydroxycholecalciferols; D002762:Cholecalciferol; D013311:Streptozocin; D002118:Calcium