Effects of Vitamin D and Its Metabolites on Calcium Transport in the Diabetic Rat

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Abstract
Diabetic rats and matched controls were studied 5 days after streptozotocin injection, matched to determine whether depressed duodenal Ca absorption associated with uncontrolled diabetes in the rat would respond to vitamin D or its metabolites. At the appropriate time following the i.v. injection of 0.25 .mu.g of either vitamin D3, 25-hydroxycholecalciferol (25-OHD3), 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) or 1.alpha.-hydroxycholecalciferol (1.alpha.-OHD3) to half of each diabetic and control group, Ca transport was evaluated using everted duodenal sacs with 0.4 mM 40Ca and tracer 45Ca on both mucosal and serosal surfaces. All agents stimulated duodenal Ca absorption in controls. Diabetics responded only to 1,25-(OH)2D3, the metabolite that acts directly on the duodenum, and to its synthetic analog, 1.alpha.-OHD. 1.alpha.-OHD3 is activated to 1,25-(OH)2D3 by 25-hydroxylation in the liver; 25-OHD3 must be 1.alpha.-hydroxylated in the kidney to be active. The stimulation of duodenal Ca absorption in diabetic rats by 1.alpha.-OHD3, but not by either vitamin D3 or 25-OHD3, is most consistent with a defect in vitamin D metabolism at the 1.alpha.-hydroxylation step in the kidney.