Effect of chronic vitamin D infusion upon in vivo glucose disposal

We have previously demonstrated that parathyroid hormone (PTH) infusion dec reases glucose disappearance rate (K-g) in vivo. Because in the rodent mode l used it was not possible to determine whether the PTH itself, the induced hypercalcemia, or both contributed to the glucose intolerance, we examined the effect of vitamin D infusion on insulin-mediated glucose disposal. Ln this model also hypercalcemia is induced but PTH levels are suppressed. Thi rty male Sprague Dawley rats were continuously infused with vit D for 5 day s using an Alzet miniosmotic pump, at a rate of 9.7 pmol/hour. Thirty contr ols were infused with the vehicle alone. On the 5th day, glucose 700 mg/kg and insulin 0.35 U/kg were given as a bolus through the left femoral vein a nd blood samples were obtained from the fight femoral vein just prior to an d at 2, 5, 10, and 20 minutes post-glucose/insulin infusion. At the end of 5 days, plasma calcium levels were higher in the vit D-infused rats than in the control rats (12.8 +/- 0.1 versus 10.0 +/- 0.1 mg/dL, P < 0.01) and ra t PTH levels were suppressed (2.1 +/- 0.1 versus 62 +/- 12 pg/ml, P < 0.01) . Glucose levels were higher in the vit D animals only at 5 minutes followi ng glucose/insulin bolus (375 +/- 7 versus 350 +/- 6 mg/dL, P < 0.01) but a t no other time. There were no differences between serum insulin levels at any time. Unlike previous findings in PTH-infused rats, K-g (measured from 2 to 20 minutes following glucose/insulin bolus) was not different between groups (4.5 +/- 0.3 versus 4.7 +/- 0.2, P = 0.92.) A positive correlation b etween serum calcium and serum glucose was found only at 5 minutes (r = 0.5 5, P < 0.01) and only in the vit D animals. The areas under the glucose cur ves approached statistically significant differences (vit D-infused 5258 +/ - 142 mg/dL/18 minutes versus control 4947 +/- 127, P = 0.06,) Analysis of serum glucose data by two-factor analysis of variance (ANOVA) suggests that the two groups differ slightly in glucose values (P = 0.03) but have paral lel K-g. In order to define whether different effects of PTH (1-34) and vit D on intracellular calcium [Ca2+](i) levels could partly explain the diffe rent effects of PTH and vit D infusion on glucose disposal, we investigated the effect of PTH and vit D infusions on basal and concanavalin A (con A)- stimulated changes in mononuclear [Ca+2](i) levels. Following 5 days of PTH , vit D, or control infusion, peripheral mononuclear cells were incubated w ith 50 mu g/ml con A. Changes in [Ca+2](i) over 5 minutes were calculated b y flow cytometric measurement of the calcium sensitive fluo-3 AM dye. Despi te achieving significant and comparable degrees of hypercalcemia in the PTH and vit D infused animals, there were no differences in basal or con A-sti mulated [Ca+2](i) levels from control. Consequently, we conclude that vit D -induced hypercalcemia associated with suppressed PTH levels has mild affec ts on glucose homeostasis but does not affect glucose disappearance rate in vivo (K-g) as does hypercalcemia induced by PTH infusion, that neither chr onic PTH infusion nor chronic vit D infusion are associated with long-stand ing changes in [Ca2+](i) levels.