Renal antioxidant enzyme mRNA levels are increased in rats with experimental diabetes mellitus

Exposure to high glucose concentrations increases the mRNA levels of oxygen radical scav- enging enzymes in cultured endothelial cells, suggest- ing a compensatory response to increased free radical production. To test the hypothesis that this response also occurs in vivo, Cu,Zn-superoxide dismutase (Cu,Zn-SOD) and catalase mRNA levels, were mea- sured in the kidneys of Sprague-Dawley rats 17 days after intravenous injection of streptozotocin (60 mg/ kg body weight) and compared with those of control rats. Diabetic rats were either left untreated or given differing insulin regimens (2, 3–8, 6–10 IU/day) in two different experiments that were designed to achieve varying degrees of metabolic control. Cu,Zn-SOD and catalase mRNA levels were mea- sured by Northern blot hybridization and standard- ized by 28S ribosomal RNA determination. Re- nal Cu,Zn-SOD and catalase mRNA levels were significantly greater in untreated diabetic and in low- dose (2 IU/day) insulin-treated rats than in controls. Treatment with a moderate dose (3–8 IU/day) of in- sulin normalized catalase but not Cu,Zn-SOD mRNA levels. The highest insulin regimen (6–10 IU/ day), in addition to achieving complete metabolic control as evidenced by normal growth and plasma glucose levels, normalized both catalase and Cu,Zn- SOD mRNA levels. Thus, in rats with streptozoto- cin-induced diabetes Cu,Zn-SOD and catalase renal mRNA levels are greater than in normal rats. This difference is prevented by sufficient insulin dosage to normalize plasma glucose and might be due to an increased production of free radicals.