Increased Glomerular Cytosolic Phospholipase A2 Activity of OLETF Rats with Early Diabetes

In view of the potential role of prostaglandins (PGs) in development of glomerular hyperfiltration leading to diabetic nephropathy, we studied the temporal relationship of the activity of cytosolic phospholipase A(2) (cPLA(2)), a rate-limiting enzyme for eicosanoid biosynthesis, with hyperfiltration and the histological changes in glomeruli using OLETF rats, a model for non-insulin-dependent diabetes mellitus (NIDDM). Diabetes mellitus and associated histopathological changes, which developed spontaneously by 30-46 weeks after birth of OLETF rats, were accompanied by approximately 65% increase in glomerular cPLA(2) activity that showed significant correlations with elevated plasma glucose levels and creatinine clearance. Moreover, mesangial cells cultured for 5 days with high glucose exhibited approximately 2-fold higher cPLA(2) activity than those cultured with physiologic level of glucose. These data suggest that increased glomerular cPLA(2) activity leads to production of PGs, which may promote the progression of early diabetic glomerular hyperfiltration and subsequent diabetic nephropathy.