Inhibition of somatomedin-like activity by serum from streptozotocin-diabetic rats: Prevention by insulin treatment and correlation with skeletal growth

Diabetes mellitus was induced in rats by streptozotocin. This gave rise to a loss of somatomedin activity in serum. The loss of somatomedin activity was due to the presence of inhibitors associated with serum proteins having mol wts of less than 1,1-10, 30-50, and 300 K. Whereas less than 1, 1-10, and 30-50 kilodalton fractions were not inhibitory in control and insulin-treated animals, greater than 300 kilodalton fraction was inhibitory in control and insulin-treated animals; the inhibitory activity of this fraction in diabetic animals was significantly greater than that in controls and insulin-treated animals. The appearance of these inhibitors in diabetic animals was accompanied by reduced skeletal growth. Treatment of diabetic animals with insulin abolished the somatomedin-inhibitory activity of serum and corrected the skeletal growth deficit. Serum inhibitors of somatomedin may, therefore, be involved in the causation of some of the complications of diabetes, including impaired skeletal growth.