Role of Insulin in the Increase in Serum 1,25- Dihydroxyvitamin D Concentrations in Response 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.

Association of increased renal <i>Cyp24a1</i> gene expression with low plasma 1,25-dihydroxyvitamin D levels in rats with streptozotocin-induced diabetes

“…Furthermore, STZ rats had low body weight and high levels of food intake volume, plasma glucose, plasma corticosterone and 24 h urine volume (5 ml/24 h vs 213 ml/24 h for control and STZ rats, respectively), as previously reported. (18,19) Plasma BUN levels were higher in STZ rats than the control. On the other hand, plasma creatinine levels were similar between control and STZ rats.…”

Drug and Hormone Effects on Vitamin D Metabolism

“…Insulin may also play an important role in the stimulation of renal 1,25(OH) 2 D synthesis in response to phosphate deprivation. In streptozotocindiabetic rats, 1,25(OH) 2 D rose only slightly following phosphate deprivation, as compared with a marked response in rats replaced with insulin [175]. Decreased serum vitamin-D-binding protein (DBP) has also been reported in experimentally induced diabetic rats, resulting in decreased total 1,25(OH) 2 D and normal free 1,25(OH) 2 D [176].…”

Effects of a vitamin D3 analog on diabetes in the bio breeding (BB) rat

“…Moreover, there is substantial disagreement with regard to the effects of the administration of oral insulin with adjuvants [Matsumoto et al, 1986;Hartmann et al, 1997;Kolb et al, 1997;Bellmann et al, 1998;Buschard et al, 2000]. Therefore, we observed the effects of a vitamin D 3 analog and insulin treatment in the BB rat model.…”