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The expression of catalase (CAT), CuZn superoxide-dismutase (CuZnSOD), glutathione peroxidase (GPX), and Mn superoxide-dismutase (MnSOD) mRNA was quantified in peripheral blood mononuclear cells\u2014obtained from 26 patients with type 1 diabetes and nephropathy, 15 with no microvascular complications after 20 years\u2019 duration of diabetes, and 10 normal healthy control subjects\u2014that were exposed in vitro to hyperglycemia (HG) (31 mmol\/l d-glucose). Under HG, there was a twofold increase in the expression of CAT, CuZnSOD, and GPX mRNA in the patients without complications and the control subjects versus patients with nephropathy (P &amp;lt; 0.0001), and MnSOD did not change in any of the groups. The aldose reductase inhibitor zopolrestat partially restored the levels of CAT, CuZnSOD, and GPX mRNA in the patients with nephropathy (P &amp;lt; 0.05). There was a highly significant correlation between increased aldose reductase (ALR2) expression, CAT, CuZnSOD, and GPX mRNA levels under HG conditions and polymorphisms of ALR2 in the patients with nephropathy (P &amp;lt; 0.00001). In conclusion, these results suggest that high glucose flux through aldose reductase inhibits the expression of antioxidant enzymes.<\/jats:p>","DOI":"10.2337\/diabetes.52.3.846","type":"journal-article","created":{"date-parts":[[2007,3,6]],"date-time":"2007-03-06T19:04:22Z","timestamp":1173207862000},"page":"846-851","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":93,"title":["The Response of Antioxidant Genes to Hyperglycemia Is Abnormal in Patients With Type 1 Diabetes and Diabetic Nephropathy"],"prefix":"10.2337","volume":"52","author":[{"given":"Andrea D.","family":"Hodgkinson","sequence":"first","affiliation":[{"name":"Department of Molecular Medicine, Peninsula Medical School, Plymouth, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tracey","family":"Bartlett","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Peninsula Medical School, Plymouth, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter J.","family":"Oates","sequence":"additional","affiliation":[{"name":"Pfizer Global Development, Groton, Connecticut"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beverley A.","family":"Millward","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Peninsula Medical School, Plymouth, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew G.","family":"Demaine","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Peninsula Medical School, Plymouth, U.K"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","reference":[{"key":"2022031215423421600_R1","doi-asserted-by":"crossref","unstructured":"The Diabetes Control and Complications Trial Research Group: The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. 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