Improved vascular function upon pioglitazone treatment in type 2 diabetes is not associated with changes in mononuclear NF-κB binding activity

G. Rudofsky, P. Reismann, I. A. Grafe, I. Konrade, Z. Djuric, J. Tafel, S. Buchbinder, M. Zorn, P. M. Humpert, A. Hamann, M. Morcos, P. P. Nawroth, A. Bierhaus

Research output: Contribution to journalArticlepeer-review

10 Citations (Scopus)

Abstract

Thiazolidinediones such as pioglitazone have been shown to exert anti-inflammatory effects independent of their insulin sensitizing effects by reducing activation of the proinflammatory transcription factor NF-κB in animal models of experimental diabetes. Furthermore, short-term pioglitazone treatment ameliorates endothelial dysfunction in conduit arteries of patients with type 2 diabetes. Since inflammation is supposed to impair flow-mediated vasodilatation, we studied the effects of an 8-week pioglitazone intervention on endothelial function and mononuclear NF-κB activation in patients with type 2 diabetes. Twenty patients were included in a randomized, double-blind, placebo-controlled study receiving 30 mg pioglitazone or placebo, respectively. Flow-mediated endothelium dependent vasodilatation (FMD) of the brachial artery, NF-κB binding activity in peripheral blood mononuclear cells [pBMC, determined by electrophoretic mobility shift assay (EMSA)] and interleukin-6 (IL-6)-transcription rates (determined by real-time PCR) were measured at study entry and after eight weeks of intervention. Pioglitazone treatment resulted in a significant improvement of FMD (4.3%±3.3; p=0.003), while no effect was seen under placebo medication (2.0%±2.7; p=0.71). The correction of FMD was neither paralleled by a pioglitazone-dependent reduction in mononuclear NF-κB binding activity (ΔNF-κB activity: pioglitazone: 9.2%±6.7, p=0.24; placebo: 5.7%±19.6; p=0.82) nor in NF-κB dependent gene transcription as determined for IL-6 (AIL-6 pioglitazone: +1.8%±12.0, p=0.93; placebo: -0.2%±9.7; p=0.92). These data demonstrate for the first time that pioglitazone treatment improves endothelial dysfunction in patients with type 2 diabetes without affecting NF-κB binding activity and NF-κB dependent proinflammatory gene expression in pBMC.

Original languageEnglish
Pages (from-to)665-671
Number of pages7
JournalHormone and Metabolic Research
Volume39
Issue number9
DOIs
Publication statusPublished - Sep 2007
Externally publishedYes

Keywords

  • Endothelial function
  • Flow-mediated vasodilatation
  • NF-κB activity
  • Pioglitazone
  • Type 2 diabetes

Field of Science

  • 3.2 Clinical medicine

Publication Type

  • 1.1. Scientific article indexed in Web of Science and/or Scopus database

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