Effect of somatomedin C on insulin-sensitive phosphodiesterase in rat fat cells.

Membrane-bound low-Km cAMP phosphodiesterase (PDE) was activated when intact rat fat cells were incubated with somatomedin C. Somatomedin C rapidly stimulated the enzyme, reaching a maximum reaction in 5 to 10 minutes. By kinetic analysis, somatomedin C activated PDE by increasing the maximal velocity (Vmax) values without altering the Michaelis-Menten constant (Km) values (0.24 +/- 0.03 mumol/L). The ED50 value of the activation by somatomedin C was very high (38.0 +/- 3.2 nmol/L) compared with that of insulin (0.22 +/- 0.07 nmol/L). This indicates that somatomedin C was about 173 times less potent than insulin in the stimulation of PDE. This potency ratio is similar to those that have been reported on lipid formation or on the other biologic insulinlike activities. When the insulin receptors were destroyed by trypsin treatment, effects of somatomedin C on the enzyme activation were abolished. This finding suggests that activation of PDE by somatomedin C was mediated through the insulin receptor.