Decreased Phospholipase A₂ Activity in Plasma and Liver in Uncontrolled Diabetes Mellitus: A Defect in the Early Steps of Prostaglandin Synthesis?

Arachidonic acid metabolites and prostaglandins participate in numerous physiologic functions. An enzyme important in the control of prostaglandin production is phospholipase A₂. In this study, we have investigated the changes in plasma and hepatic phospholipase A₂ activity in diabetes mellitus. In uncontrolled diabetic patients, the postheparin plasma phospholipase A₂ level was 18.7 ± 4,1 U/ml; this value was significantly different from the enzyme activities in control subjects (106 ± 9.8 U/ml) and in controlled diabetic patients (87 ± 7.3 U/ml). In the streptozocin-induced diabetic rat model, the postheparin plasma phospholipase A₂ level (1.9 ± 0.45 U/ml) was also decreased when compared with normal (9.4 ±1.6 U/ml) and controlled diabetic rats (7.0 ± 1.3 U/ml). The total hepatic enzyme activity in the uncontrolled diabetic rats was only 21.6% of that seen in control rats. Subcellular fraction studies demonstrated that the enzyme activity is decreased in all fractions in the liver. Liver perfusion studies showed that the heparin-releasable phospholipase A₂ activity in the perfusate was significantly decreased in the diabetic rats when compared with control and controlled diabetic animals. We conclude that postheparin plasma and hepatic phospholipase A₂ activities are decreased in uncontrolled diabetes mellitus, that the low plasma activity is related to decreased release from the liver, and that the alterations in phospholipase A₂ activity in plasma and liver are restored to normal by controlling the diabetic status.