Observations of a growth hormone-resistant decrease in somatomedin activity associated with conditions of insulinopenia suggest that somatomedin and growth might be related to metabolic control in diabetes mellitus. We examined this relationship by comparing measures of insulin effect with serum somatomedin activity (porcine cartilage bioassay), cartilage growth activity (SO4 uptake in vitro), and change in body weight in streptozotocin-diabetic rats. A range of metabolic control was produced by administration of varied quantities of insulin over twoand four-day periods. Serum somatomedin activity was significantly correlated with serum glucose and Β-hydroxybutyrate (r = −0.69 and −0.76, respectively, p <0.001 for both) but not with free fatty acids. A level of serum glucose <240 mg./dl. or /3-hydroxybutyrate <1.3 mM at sacrifice was generally associated with serum somatomedin activity within the normal range. Urine glucose levels less than 0.1 gm./24 hr. were also associated with normal serum somatomedin activity. Insulin therapy sufficient to provide β-hydroxybutyrate less than 1.3 mM at sacrifice was associated with levels of serum somatomedin activity and cartilage growth activity comparable to those of normal animals and significantly greater than those of untreated diabetic animals. This level of insulin effect also permitted diabetic animals to gain weight at a rate comparable to that of normal animals.
These studies demonstrate a close relationship between insulin efficacy, serum somatomedin activity, cartilage growth activity, and weight gain and support the hypothesis that through somatomedin, insulin may contribute to growth.