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

AbstractWe 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

The effects of bed rest and countermeasure exercise on the endocrine system in male adults: Evidence for immobilization-induced reduction in sex hormone-binding globulin levels

Background and Aim. There is limited data on the effects of inactivity (prolonged bed-rest) on parameters of endocrine and metabolic function; we therefore aimed to examine changes in these systems during and after prolonged (56-day) bed-rest in male adults. Subjects and Methods. 20 healthy male subjects underwent 8 weeks of strict bed-rest and 12 months follow-up as part of the Berlin Bed-Rest Study. Subjects were randomised to an inactive group or a group that performed resistive vibration exercise (RVE) during bed-rest. All outcome parameters were measured before, during and after bed-rest. These included body composition (by whole body dual X-ray absorptiometry), sex hormone-binding globulin (SHBG), testosterone (T), estradiol (E2), prolactin (PRL), cortisol (C), thyroid stimulating hormone (TSH) and free triiodothyronine (FT3). Results. Serum SHBG levels decreased in inactive subjects but remained unchanged in the RVE group (p<.001). Serum T concentrations increased during the first 3-weeks of bed-rest in both groups (p<.0001), while E2 levels sharply rose with re-mobilisation (p<.0001). Serum PRL decreased in the CTRL group but increased in the RVE group (p=.021). C levels did not change over time (p≥.10). TSH increased whilst FT3 decreased during bed-rest (p all≤.0013). Conclusions. Prolonged bed-rest has significant effects on parameters of endocrine and metabolic function, some of which are related to, or counteracted by physical activity

Resistive vibration exercise attenuates bone and muscle atrophy in 56-days of bed-rest: whole body DXA and biochemical markers of bone metabolism

Summary During and after prolonged bed rest, changes in bone metabolic markers occur within 3 days. Resistive vibration exercise during bed rest impedes bone loss and restricts increases in bone resorption markers whilst increasing bone formation. Introduction To investigate the effectiveness of a resistive vibration exercise (RVE) countermeasure during prolonged bed rest using serum markers of bone metabolism and whole-body dual X-ray absorptiometry (DXA) as endpoints. Methods Twenty healthy male subjects underwent 8 weeks of bed rest with 12 months follow-up. Ten subjects performed RVE. Blood drawings and DXA measures were conducted regularly during and after bed rest. Results Bone resorption increased in the CTRL group with a less severe increase in the RVE group (p = 0.0004). Bone formation markers increased in the RVE group but decreased marginally in the CTRL group (p < 0.0001). At the end of bed rest, the CTRL group showed significant loss in leg bone mass (−1.8(0.9)%, p = 0.042) whereas the RVE group did not (−0.7(0.8)%, p = 0.405) although the difference between the groups was not significant (p = 0.12). Conclusions The results suggest the countermeasure restricts increases in bone resorption, increased bone formation, and reduced bone loss during bed rest