Insulin markedly potentiates the capacity of parathyroid hormone to increase expression of 25-hydroxyvitamin D3-24-hydroxylase in rat osteoblastic cells in the presence of 1,25-dihydroxyvitamin D3.

We have previously shown that insulin alters the renal metabolism of 25-hydroxyvitamin D. To examine the effect of insulin on vitamin D metabolism in bone, we have used UMR-106 osteoblast-like cells to study the regulation of 25(OH)D3-24-hydroxylase (24-hydroxylase) expression by insulin. The 24-hydroxylase is an important enzyme in degrading 1,25-dihydroxyvitamin D3 (1,25(OH)2D) in target tissues. Insulin alone had no effect on mRNA levels of the cytochrome P450 component (CYP24) of the 24-hydroxylase or on 24-hydroxylase activity itself in UMR cells. However, insulin increased the capacity of parathyroid hormone (PTH) to elevate CYP24 mRNA levels by 3-4-fold and to increase 24-hydroxylase activity by 2-fold in the presence of 1,25(OH)2D. Insulin increased the maximal responsiveness of UMR cells to PTH without altering their sensitivity. The action of insulin required the presence of 1,25(OH)2D and was partly dependent on new protein synthesis. Insulin-like growth factor 1 also potentiated the effects of PTH. This marked stimulation of the 24-hydroxylase by PTH and insulin may serve to regulate 1,25(OH)2D action and/or to produce 24,25-dihydroxyvitamin D in bone cells.