Characterization of the Effect of Insulin on Collagen Synthesis in Fetal Rat Bone*

Publisher Website
Google Scholar
Abstract
The effect of insulin on collagen synthesis in 21 day old fetal rat calvaria maintained in organ culture was characterized. All experiments were done in the presence of 100 mg/dl glucose and 3 mM phosphate, which were optimal concentrations for insulin responsiveness. All concentrations of insulin tested (1 nM-1 .mu.M) increased the percentage of collagen being synthesized in the central bone, whereas only high concentrations of hormone (100 nM-1 .mu.M) increased the percentage of collagen being synthesized in periosteum. Insulin at 3 nM increased the labeling of type I collagen in the central bone, but did not alter the labeling of type I or III collagen in the periosteum. Proinsulin was .apprx. 10-100 times less effective than insulin in stimulating collagen synthesis, whereas porcine relaxin and C-peptide were ineffective. Insulin did not enhance the deposition of newly synthesized collagen in the bone by a mechanism that involved decreasing the degradation of collagen. To determine whether insulin enhanced collagen synthesis by increasing the replication of collagen-synthesizing cells, the effect of insulin was tested in the presence of hydroxyurea, a DNA synthesis inhibitor. Hydroxyurea at 1 mM had little effect on collagen synthesis in control cultures or those treated with 1 or 10 nM insulin. Hydroxyurea blunted the stimulation of collagen synthesis that occurred at higher concentrations of insulin. Evidently, insulin at physiological levels appears to increase bone collagen synthesis by a direct effect on the osteoblast, insulin at high concentrations has an additional action to increase the replication of collagen-synthesizing cells.