Streptozotocin-induced diabetes in the rat has been shown to decrease and insulin to increase the activity of cyclic AMP phosphodiesterase (PDE) in adipose tissue. Protein activator (PA), a substance of low molecular weight, is essential for full activity of some component phosphodiesterases. A significant decrease in protein activator level (60% of control) is found in the 13,000 × g boiled supernatant from streptozotocin-diabetic rat adipose tissue. When diabetic animals are treated with insulin 24 h following the induction of diabetes, protein activator is restored to 80% of the normal control level; when diabetic animals are immediately treated with insulin, the levels of protein activator are not reduced (98% of control). Hence, insulin is capable of reversing both the decrease in protein activator and phosphodiesterase activity seen with diabetes. When partially purified supernatant from diabetic animal fat is chromatographed on a DEAE Sephacel column, the untreated diabetics show inhibition, whereas insulin-treated diabetics show maximal stimulation of the low Km cyclic AMP phosphodiesterase. Protein activator and an inhibitor are readily separated when adipose tissue homogenate is centrifuged at 13,000 × g and the boiled supernatant is passed over a DEAE Sephacel column.
Diabetes is associated with a decrease in both cyclic AMP phosphodiesterase and protein activator activity, both of which are restored to normal by administration of insulin. We also report the presence of an inhibitor of activator, which is increased in streptozotocin diabetes. All of these components appear to play a role in the pathophysiology of diabetes.