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- Title
Insufficient glycemic control increases nuclear factor-kappa B binding activity in peripheral blood mononuclear cells isolated from patients with type 1 diabetes.
- Authors
Hofmann, Marion A.; Schiekofer, Stephan; Kanitz, Michael; Klevesath, Martina S.; Joswig, Martina; Lee, Vong; Morcos, Michael; Tritschler, Hans; Ziegler, Reinhard; Wahl, Peter; Bierhaus, Angelika; Nawroth, Peter P.; Hofmann, M A; Schiekofer, S; Kanitz, M; Klevesath, M S; Joswig, M; Lee, V; Morcos, M; Tritschler, H
- Abstract
<bold>Objective: </bold>The redox-sensitive transcription factor nuclear factor-kappa B (NF-kappa B) is believed to contribute to late diabetic complications. It is unknown whether NF-kappa B is influenced by glycemic control.<bold>Research Design and Methods: </bold>To determine whether NF-kappa B is activated in patients with insufficient glycemic control (HbA1c > 10%), we developed a tissue culture-independent electrophoretic mobility shift assay (EMSA)-based semiquantitative detection system that allowed us to determine NF-kappa B activation in ex vivo-isolated peripheral blood mononuclear cells (PBMCs). We included 43 patients with type 1 diabetes in this cross-sectional study. 10 of those received the antioxidant thioctic acid (600 mg/day p.o.) for 2 weeks.<bold>Results: </bold>Monocytes of patients with HbA1c levels > 10% demonstrated significantly higher NF-kappa B binding activity in an EMSA and a stronger NF-kappa B staining in immunohistochemistry than monocytes of patients with HbA1c levels of 6-8%. The increase in NF-kappa B activation correlated with an increase in plasmatic markers of lipid peroxidation. Treatment with the antioxidant thioctic acid decreased NF-kappa B binding activity.<bold>Conclusions: </bold>Hyperglycemia induces activation of the transcription factor NF-kappa B in ex vivo-isolated PBMCs of patients with type 1 diabetes. NF-kappa B activation is at least partially dependent on oxidative stress, since the antioxidant thioctic acid significantly lowered the extent of NF-kappa B binding activity.
- Publication
Diabetes Care, 1998, Vol 21, Issue 8, p1310
- ISSN
0149-5992
- Publication type
journal article
- DOI
10.2337/diacare.21.8.1310