Insufficient Glycemic Control Increases Nuclear Factor-κB Binding Activity in Peripheral Blood Mononuclear Cells Isolated From Patients With Type 1 Diabetes

  1. Peter P Nawroth, MD
  1. Department of Medicine, University of Heidelberg Heidelberg
  2. ASTA Medica Frankfurt am Main, Germany
  1. Address correspondence and reprint requests to Peter P Nawroth, MD, University of Heidelberg, Department of Internal Medicine I, Bergheimer Str. 58, 69115 Heidelberg, Germany. E-mail: peter_nawroth{at}krzmail.krz.uni-heidelberg.de

Abstract

OBJECTIVE The redox-sensitive transcription factor nuclear factor-kB (NF-kB) is believed to contribute to late diabetic complications. It is unknown whether NF-kB is influenced by glycemic control.

RESEARCH DESIGN AND METHODS To determine whether NF-kB 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-kB 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-kB binding activity in an EMSA and a stronger NF-kB staining in immunohistochemistry than monocytes of patients with HbA1c levels of 6–8%. The increase in NF-kB activation correlated with an increase in plasmatic markers of lipid peroxidation. Treatment with the antioxidant thioctic acid decreased NF-kB binding activity.

CONCLUSIONS Hyperglycemia induces activation of the transcription factor NF-kB in ex vivo-isolated PBMCs of patients with type 1 diabetes. NF-kB activation is at least partially dependent on oxidative stress, since the antioxidant thioctic acid significantly lowered the extent of NF-kB binding activity.

  • Received November 25, 1997.
  • Accepted April 15, 1998.
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