Nutrition and somatomedin. XV. Growth plate, growth factor and biologically active somatomedins in rats with streptozotocin-induced diabetes.
Diabetic children may exhibit poor growth, yet levels of growth hormone and somatomedins measured by specific radioligand assays usually are normal. In the present studies, biological assays based on costal cartilage from hypophysectomized rats were used to test the possibility that diabetes is associated with decreases in circulating growth-related factors. 'Growth plate growth factor' activity was evaluated with tissue from the osteochondral junction (which resembles epiphyseal cartilage), and 'somatomedin' activity was measured with resting cartilage distant from the growth plate. Diabetes was induced in rats by administration of streptozotocin (STZ) at 40, 80, 160 and 310 mg/kg. Two days later, animals receiving STZ 40 mg/kg exhibited slight hyperglycemia but normal beta-hydroxybutyrate and weight gain; glucose and beta-hydroxybutyrate rose, and weight fell progressively with higher dosage. Gel filtration on Sephadex G-75 at pH 2.4 was used to separate rat serum into somatomedins (KAv 0.50-0.75) and growth plate growth factor (KAv 0.38-0.50). Somatomedins were 102, 92, 83 and 68% of control in STZ-treated animals, i.e. unchanged from control at 40 mg/kg STZ and falling only with higher dosage. In contrast, the growth plate growth factor declined at all doses of STZ to 93, 84, 69 and 57% of control. Thus, the growth plate growth factor began to fall with mild hyperglycemia alone (glucose 190 mg/dl), while a comparable fall in somatomedins was not seen until glucose was greater than 400 mg/dl and beta-hydroxybutyrate was three times normal. Only the growth plate growth factor was correlated with changes in body weight (r = 0.44, p less than 0.025). We conclude that decreases in levels of a circulating growth plate growth factor may contribute to growth impairment in diabetes. Measurements of this factor may be useful in examining underlying mechanisms.