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

Marion A Hofmann; Stephan Schiekofer; Michael Kanitz; Martina S Klevesath; Martina Joswig; Vong Lee; Michael Morcos; Hans Tritschler; Reinhard Ziegler; Peter Wahl; Angelika Bierhaus; Peter P Nawroth

doi:10.2337/diacare.21.8.1310

Original Articles

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

Marion A Hofmann, MD,
Stephan Schiekofer, MD,
Michael Kanitz,
Martina S Klevesath, MD,
Martina Joswig, MD,
Vong Lee, MD,
Michael Morcos, MD,
Hans Tritschler, PHD,
Reinhard Ziegler, MD,
Peter Wahl, MD,
Angelika Bierhaus, PHD and
Peter P Nawroth, MD

Department of Medicine, University of Heidelberg Heidelberg
ASTA Medica Frankfurt am Main, Germany

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

Diabetes Care 1998 Aug; 21(8): 1310-1316. https://doi.org/10.2337/diacare.21.8.1310

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 (HbA_1c > 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 HbA_1c 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 HbA_1c 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.