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T Adachi, M Inoue, H Hara, E Maehata, and S Suzuki

Extracellular-superoxide dismutase (EC-SOD) is a secretory glycoprotein located in blood vessel walls at high levels and may be important in the antioxidant capability of vascular walls. The aim of this study was to assess plasma levels of EC-SOD and to evaluate the relationship of the EC-SOD level with insulin resistance in type 2 diabetic patients. We determined plasma EC-SOD in 122 patients and found for the first time that the EC-SOD level was strongly and positively related to adiponectin (r=0.503, P < 0.001), and significantly and inversely related to fasting plasma glucose (FPG) (r=-0.209, P=0.022), body-mass index (BMI) (r=-0.187, P=0.040) and homeostasis model assessment-insulin resistance index (HOMA-R) (r=-0.190, P=0.039). Stepwise-multiple regression analysis also showed a significant influence of adiponectin (F=33.27) on the EC-SOD level. Administration of pioglitazone to 19 diabetic patients significantly increased the plasma levels of EC-SOD (69.9+/-19.3 ng/ml to 97.4+/-25.9 ng/ml; P < 0.0001) and adiponectin, while it decreased tumor necrosis factor-alpha (TNF-alpha). The present observations suggest that factors related to the pathogenesis of insulin resistance play an important role in the regulation of the plasma EC-SOD concentration. It is possible that the increase in the EC-SOD level by pioglitazone administration in diabetic patients is due to a decline of TNF-alpha, which is known to suppress EC-SOD expression.