Effect of insulin administration on bone formation is impaired in rats with skeletal unloading

The effect of insulin administration on bone formation was investigated in the femoral diaphysis of rats with skeletal unloading. When the femoral-diaphyseal tissues from normal rats were cultured in the presence of insulin (10(-9) and 10(-8) M) for 48 h, the hormone produced a significant increase of alkaline phosphatase activity, collagen, deoxyribonucleic acid (DNA) and calcium contents in the bone tissues, indicating that it has a direct stimulatory effect on bone formation. Moreover, when normal rats received a subcutaneous administration of insulin (5.0 IU/100 g body weight) 5 times at 24-h intervals, the hormone caused a significant increase of alkaline phosphatase activity, DNA and calcium contents in the femoral diaphysis. Those increases were not seen by insulin administration to the skeletal-unloading rats with hindlimb hang for 4 d. The present results indicate that the stimulatory effect of insulin on bone formation is lost by skeletal unloading. The finding further supports the view that insulin impairment plays an important role in the deterioration of bone formation by microgravity.