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

Abstract

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.

The effects of intermittent administration of human parathyroid hormone (1–34) on streptozotocin-induced diabetic rats

“…However, it has not yet been clearly determined why diabetes mellitus causes a reduction in bone mass. Schneider et al [25] and Spencer [26] observed depressed Ca resorption from the intestine, reduction of Ca-binding protein activity, increase in serum PTH level, and decrease in renal 25-hydroxyvitamin D-l-hydroxylase activity in diabetes mellitus. In the current study, STZ-induced diabetes mellitus showed osteoporosis, confirmed by reductions in dry weight, ash weight, and calcium and phosphoros content of the femurs, and of bone volume in bone histomorphometry of the tibias.…”

Effects of Diabetes on Calcium-Binding Protein in the Cecum and Colon of the Rat

“…Dia betic rats show other evidence for vitamin D deficiency including decreased duodenal [3,15,16] and cecal and colonic [9] calcium transport in comparison with controls. The depression of calcium transport in diabetes is also the result of deficiency of l,25-(OH)2D since the transport defect is corrected by ad ministration of l,25-(OH)2D [17], and by in sulin treatment [16], which restores 1,25-(OH)2D to normal in diabetes [1], Based on our previous study of vitamin D metabolites in diabetes [1], the present study shows that CaBP of cecum and colon re sponds to lower levels of serum 1,25-dihydroxyvitamin D in the diabetic state. The depression is not as great as in duodenum where CaBP specific activity at 5 days of dia betes is one-third that of controls [4], At 12 days of diabetes, growth of cecum overcomes the depressed CaBP per unit of mucosa to nearly maintain total activity, while colonic CaBP of diabetes remains depressed in both total and specific activity.…”

Hypercalcemic effect of insulin in thyroparathyroidectomized alloxan-treated rats.

“…Lack of insulin led to hypercalciuria Schedl, 1972 andSchneider et al, 1976) which has been felt to result from osmotic diuresis caused by glycosuria (Massry et al, 1973 andMonnier et al, 1978). Increased urinary calcium excretion may be one possible cause of negative calcium balance in diabetes (Wood et al, 1984).…”

“…Disturbances in calcium metabolism which have been demonstrated in both experimental insulin-deficient rats (Ramamurthy et al, 1973;Schedl et al, 1978;Hough et al, 1982 andWongsurawat et al, 1983) and diabetic patients (Fogh-Andersen et al, 1982 and have been attributed to the decrease in levels of 25(OH)D and 24, 25(OH)2D (Ishida et al, 1983(Ishida et al, , 1985 and impairment of renal, 1, 25(OH)2D3 production (Schneider et al, 1976;1977a andWongsurawat et al, 1983). Such long term disturbances may result in negative calcium balance which can be reversed by insulin treatment.…”