MECHANISM OF DECREASED ARACHIDONIC-ACID IN THE RENAL-CORTEX OF RATS WITH DIABETES-MELLITUS

The purpose of this study was to investigate the roles of decreased synthesis and increased consumption in the depression of arachidonic acid levels in renal cortex and glomeruli of rats with streptozotocin-induced diabetes mellitus. In diabetic rats, arachidonic acid was depressed 33.2% in renal cortex, 47.4% in liver and 66.1% in heart compared to values of control rats. DELTA6 Desaturase activity was depressed in renal cortex, liver and heart of diabetic rats to 53.3, 55.5 and 63.7%, respectively, of control values. DELTA5 Desaturase activity was also depressed 43.7, 55.5 and 47.6% in renal cortex, liver and heart of diabetic rats, respectively. In other rats the activities of five enzymes involved in the synthesis and esterification of arachidonic acid were measured in renal cortex and in isolated glomeruli. Both tissues from diabetic rats showed depressed activities of DELTA5 and DELTA6 desaturases, increased activities of long-chain acyl-CoA synthetase and 1-acyl-sn-glycero-3-phosphocholine acyltransferase and no change in the activity of elongase as compared to those in control tissues. Malondialdehyde, an end product of lipid peroxidation, was lower in the renal cortex of diabetic rats than in control rats, whereas beta-oxidation of linoleic acid and arachidonic acid were similar in diabetic and in control rats. Basal and stimulated prostaglandin E2 synthesis were significantly higher in isolated glomeruli from diabetic rats compared to those in control rats. In isolated tubules, prostaglandin E2 synthesis was similarly low in both groups. From these data we conclude that the reduced level of arachidonic acid esterified in lipids of the kidney cortex is caused principally by depressed synthesis of arachidonic acid secondary to decreased activity of DELTA5 and DELTA6 desaturases. Increased consumption of arachidonic acid to support prostaglandin synthesis may have contributed to the depression of arachidonic acid in glomeruli but not in tubules.