Insufficient glycemic control increases nuclear factor-kappa B binding activity in peripheral blood mononuclear cells isolated from patients with type 1 diabetes.
OBJECTIVE
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Department of Medicine, University of Heidelberg, Germany.
M A
MA
Hofmann
S
S
Schiekofer
M
M
Kanitz
M S
MS
Klevesath
M
M
Joswig
V
V
Lee
M
M
Morcos
H
H
Tritschler
R
R
Ziegler
P
P
Wahl
A
A
Bierhaus
P P
PP
Nawroth
D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism*; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000097:blood*; D003929:Diabetic Neuropathies / Q000097:blood; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D066298:In Vitro Techniques; D007963:Leukocytes, Mononuclear / Q000378:metabolism*; D015227:Lipid Peroxidation; D016328:NF-kappa B / Q000378:metabolism*; D009687:Nuclear Proteins / Q000097:blood; D012044:Regression Analysis; D008063:Thioctic Acid / Q000627:therapeutic use
D000975:Antioxidants; D015415:Biomarkers; D001786:Blood Glucose; D006442:Glycated Hemoglobin; D016328:NF-kappa B; D009687:Nuclear Proteins; D008063:Thioctic Acid