RENAL ANTIOXIDANT ENZYME MESSENGER-RNA LEVELS ARE INCREASED IN RATS WITH EXPERIMENTAL DIABETES-MELLITUS

Exposure to high glucose concentrations increases the mRNA levels of o xygen radical scavenging enzymes in cultured endothelial cells, sugges ting a compensatory response to increased free radical production. To test the hypothesis that this response also occurs in vivo, Cu,Zn-supe roxide dismutase (Cu,Zn-SOD) and catalase mRNA levels, were measured i n the kidneys of Sprague-Dawley rats 17 days after intravenous injecti on of streptozotocin (60 mg/kg body weight) and compared with those of control rats. Diabetic rats were either left untreated or given diffe ring insulin regimens (2, 3-8, 6-10 IU/day) in two different experimen ts that were designed to achieve varying degrees of metabolic control. Cu,Zn-SOD and catalase mRNA levels were measured by Northern blot hyb ridization and standardized by 28S ribosomal RNA determination. Renal Cu,Zn-SOD and catalase mRNA levels were significantly greater in untre ated diabetic and in low-dose (2 IU/day) insulin-treated rats than in controls. Treatment with a moderate dose (3-8 IU/day) of insulin norma lized catalase but not Cu,Zn-SOD mRNA levels. The highest insulin regi men (6-10 IU/day), in addition to achieving complete metabolic control as evidenced by normal growth and plasma glucose levels, normalized b oth catalase and Cu,Zn-SOD mRNA levels. Thus, in rats with streptozoto cin-induced diabetes Cu,Zn-SOD and catalase renal mRNA levels are grea ter than in normal rats. This difference is prevented by sufficient in sulin dosage to normalize plasma glucose and might be due to an increa sed production of free radicals.