Urinary excretion and renal production of prostaglandins E2, F2 alpha, and thromboxane B2 in experimental diabetes mellitus.
To delineate the urinary excretion of prostaglandins E2 (PGE), F2 alpha (PGF), and thromboxane B2 (TxB) in diabetic rats, we treated male Sprague-Dawley rats with streptozocin 60 mg/kg or with vehicle. Plasma glucose and creatinine concentration and 24-hour urine collections for determination of TxB, PGE, PGF, creatinine, and protein excretion were measured at 2, 8, and 14 weeks after streptozocin. Creatinine clearance was significantly decreased in diabetic rats at 2 and 8 weeks, whereas the urinary protein excretion was three to five times that of control animals at all times. The 24-hour excretion of TxB was elevated twofold to threefold in diabetic rats, whereas PGE and PGF excretion were both significantly decreased. This alteration in excretion was not caused by increased urine flow rate, inasmuch as mannitol-induced osmotic diuresis caused an increase in PGE and PGF excretion. Eight weeks after streptozocin, a group of diabetic and control rats were sacrificed, and the production of PGE, PGF, and TxB by the renal papillae and glomeruli determined. An additional five diabetic rats were treated with protamine zinc insulin for 1 week before sacrifice to determine the effect of insulin treatment on the production of PGE, PGF, and TxB by the glomeruli and renal papillae. Papillary production of PGE, PGF, and TxB was decreased in diabetic rats, as was glomerular production of PGE and PGF. Insulin treatment increased PGF production by the renal papillae and increased PGE, PGF, and TxB production by glomeruli. These results indicate that changes in prostaglandin excretion accompany the development of marked proteinuria and a decrease in creatinine clearance.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000652:urine*; D015237:Dinoprost; D015232:Dinoprostone; D007328:Insulin / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D011458:Prostaglandins E / Q000096:biosynthesis / Q000652:urine*; D011460:Prostaglandins F / Q000096:biosynthesis / Q000652:urine*; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D013929:Thromboxane B2 / Q000096:biosynthesis / Q000652:urine*
D007328:Insulin; D011458:Prostaglandins E; D011460:Prostaglandins F; D008353:Mannitol; D013929:Thromboxane B2; D015237:Dinoprost; D015232:Dinoprostone