Journal
DIABETES CARE
Volume 28, Issue 7, Pages 1690-1697Publisher
AMER DIABETES ASSOC
DOI: 10.2337/diacare.28.7.1690
Keywords
-
Categories
Ask authors/readers for more resources
OBJECTIVE - Detective intracellular antioxidant enzyme production (IAP) has been demonstrated in adults with diabetic nephropathy. The ob objective of this study was to evaluate the effects of irbesartan, an angiotensin It receptor antagonist, on IAP in adolescents, and young adults with type 1 diabetes and early signs of retinopathy and nephropathy, RESEARCH DESIGN AND METHODS- This prospective, matched case-control study was conducted between November 2001 and December 2002 among 14 type 1 diabetic patients with early signs of angiopathy (ages 14-21 years), 11 type 1 diabetic patients without angiopathy (ages 12-22 years), and 10 healthy volunteers (ages 16-22 years). Skin fibroblasts were obtained by skin biopsies from the anterior part of the forearm and cultured in Dulbccco's modified Eagle's medium. The activity and mRNA expression of CuZn superoxide dismutase (CuZnSCD), Mn superoxide dismutase (MnSOD), catalase (CAT), and glutathione pci-ONidA, C (GPX) were measured before and after 6 months of treatment with irbesartan (150 mg/day), oil both occasions, antioxidant enzyme activity was evaluated at different glucose concentrations (5 and 22 mmol/M). RESULTS - At a normal glucose concentration (5 mmol/l), the activity and mRNA expression of CuZnSOD(0.50 +/- 0.21 units/m protein, 4.4 +/- 1.5 mRNA/glyceraldchyde-3-phosphate dehydrogenase), MnSOD (0.26 +/- 0.04 units/mg protein, 0.08 +/- 0.07 mRNA), CAT(0.32 +/- 0.08 units/mg protein, 4.8 +/- 1.3 mRNA), and GPX (0.53 +/- 0.09 units/mg protein, 2.2 +/- 0.9 mRNA) were not different among the three groups (only values of diabetic Subjects with angiopathy are shown). At high glucose concentrations, the activity and MRNA express-ion Of CuZnSOD increased similarly in all groups (diabetic subjects with angiopathy: 0.93 +/- 0.26 units/mg protein, 9.4 +/- 2.1 mRNA) that of CAT and GPX increased in only control subjects and diabetic subjects without angiopathy (diabetic subjects with angiopathy: 0.33 +/- 0.09 units/mg protein and 5.0 +/- 1.4 mRNA 0.54 +/- 0.10 units/mg protein and 2.3 +/- 1.0 mRNA, respectively). MnSOD did not change in any group. Treatment With irbesartan in adolescents with diabetic angiopathy was able to restore CAT and GPX activity and mRNA expression after exposure to high glucose concentrations. Markers of oxidative stress (serum malondialdehyde, fluorescent products of lipid peroxidation, monocyte chemoattractant protein-1, and 8-isoprostances taglandin F-2 alpha) were significantly reduced after treatment with irbesartan. CONCLUSIONS - Adolescents and young adults with early signs of diabetic angiopathy have defective intracellular antioxidant enzyme production and activity. Treatment with irbesartan call substantially improve the activity and production of these enzymes skin fibroblasts.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available