Role of insulin in the increase in serum 1,25-dihydroxyvitamin D concentrations in response to phosphorus deprivation in streptozotocin-induced diabetic rats.

Abstract

To evaluate the role of insulin in the regulation of circulating 1,25-dihydroxyvitamin D [1,25(OH)2D] levels, serum 1,25(OH)2D concentrations in response to phosphorus (P) deprivation were examined in control, streptozotocin-diabetic and insulin-treated diabetic rats. Dietary P deprivation for 1 week caused a marked increase in serum 1,25(OH)2D level from 75 +/- 4 pg/ml to 274 +/- 16 pg/ml in control rats. In contrast, serum 1,25(OH)2D level was significantly lower in diabetic rats on a normal P diet (20 +/- 2 pg/ml) compared to that in control rats and increased only slightly by P deprivation (33 +/- 4 pg/ml). Treatment of the diabetic rats on normal P diet with insulin caused an increase in serum 1,25(OH)2D concentration to a level (82 +/- 10 pg/ml) similar to that in control rats and restored the increase in serum 1,25(OH)2D concentration in response to P deprivation (315 +/- 38 pg/ml). Although there was a marked decrease in serum phosphate level by P deprivation in all groups of animals, the rise in serum calcium level by P deprivation seen in control rats was abolished in diabetic rats. In addition, while bone mineral contents decreased significantly in response to P deprivation in control rats, no significant changes in either bone calcium or P contents were observed after P deprivation in diabetic rats. Insulin treatment of the diabetic rats recovered the responsiveness to P deprivation in both serum calcium level and bone mineral contents. P deprivation did not affect plasma glucose or serum creatinine level in any group of rats. These results suggest that insulin, either directly or indirectly, is required for the increase in circulating 1,25(OH)2D concentrations in response to P deprivation, and that the rise in serum 1,25(OH)2D level may play a role in the hypercalcemic response to P deprivation.