Nutrition and Somatomedin. VI. Somatomedin Activity and Somatomedin Inhibitory Activity in Sera from Normal and Diabetic Rats*

Although serum from normal rats has somatomedin (cartilage-stimulating) activity, serum from diabetic rats often lacks somatomedin activity and can inhibit somatomedin activity when added to serum from normal rats; this is attributed to somatomedin inhibitor (s). To determine if both somatomedins and somatomedin inhibitor(s) could be present in whole serum with or without measurable somatomedin activity, somatomedin activity and somatomedin inhibitory activity were determined in rat serum after gel filtration on Sephadex G-200. Somatomedin activity was measured as the stimulation of SO4 uptake by rat cartilage in vitro, and somatomedin inhibitory activity was measured as the ability to suppress stimulation when samples were added to incubations containing serum from normal rats. At pH 7.0 (somatomedins presumably bound to carrier proteins), only somatomedin activity was found in serum from normal rats, while only somatomedin inhibitory activity was found in serum from diabetic rats. In contrast, at pH 2.4 (somatomedins presumably dissociated), somatomedin activity and somatomedin inhibitory activity were found in both sera. Serum from diabetic rats contained more somatomedin inhibitory activity and less somatomedin activity than serum from normal rats. The somatomedin inhibitory activity had an apparent molecular weight less than carrier-bound somatomedins but greater than dissociated somatomedins. These observations demonstrate that somatomedin activity in whole serum reflects the presence of both somatomedins and somatomedin inhibitor(s); decreased somatomedin activity in serum from diabetic rats appears to be due to both a decrease in somatomedins and an increase in inhibitor(s).