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

FEBS Letters

Wongsurawat, N.¹  Wongsurawat, V.J.¹  Hodam, T.L.¹  Armbrecht, H.J.¹ 

[1] Geriatric Research, Education and Clinical Center, Veterans Affairs Medical Center, St. Louis, MO 63125, USA

关键词: Insulin;    Parathyroid hormone;    24-Hydroxylase;    Vitamin D;    Osteoblast;    IGF-1;   

DOI  :  10.1016/0014-5793(96)00856-3

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown