Research article

Anti-inflammatory effect of rosiglitazone is not reflected in expression of NFκB-related genes in peripheral blood mononuclear cells of patients with type 2 diabetes mellitus

Marjolijn CE Bragt^1,2 , Jogchum Plat² , Marco Mensink² , Patrick Schrauwen² and Ronald P Mensink^1,2

¹  Nutrigenomics Consortium, Top Institute Food and Nutrition, PO BOX 557, 6700 AN Wageningen, The Netherlands

²  NUTRIM School for Nutrition, Toxicology and Metabolism, Department of Human Biology, Maastricht University Medical Centre+, PO Box 616, 6200 MD Maastricht, The Netherlands

author email corresponding author email

BMC Endocrine Disorders 2009, 9:8doi:10.1186/1472-6823-9-8

Published:	25 February 2009

Abstract

Background

Rosiglitazone not only improves insulin-sensitivity, but also exerts anti-inflammatory effects. We have now examined in type 2 diabetic patients if these effects are reflected by changes in mRNA expression in peripheral blood mononuclear cells (PBMCs) to see if these cells can be used to study these anti-inflammatory effects at the molecular level in vivo.

Method

Eleven obese type 2 diabetic patients received rosiglitazone (2 × 4 mg/d) for 8 weeks. Fasting blood samples were obtained before and after treatment. Ten obese control subjects served as reference group. The expression of NFκB-related genes and PPARγ target genes in PBMCs, plasma TNFα, IL6, MCP1 and hsCRP concentrations were measured. In addition, blood samples were obtained after a hyperinsulinemic-euglycemic clamp.

Results

Rosiglitazone reduced plasma MCP1 and hsCRP concentrations in diabetic patients (-9.5 ± 5.3 pg/mL, p = 0.043 and -1.1 ± 0.3 mg/L p = 0.003), respectively). For hsCRP, the concentration became comparable with the non-diabetic reference group. However, of the 84 NFκB-related genes that were measured in PBMCs from type 2 diabetic subjects, only RELA, SLC20A1, INFγ and IL1R1 changed significantly (p < 0.05). In addition, PPARγ and its target genes (CD36 and LPL) did not change. During the clamp, insulin reduced plasma MCP1 concentration in the diabetic and reference groups (-9.1 ± 1.8%, p = 0.001 and -11.1 ± 4.1%, p = 0.023, respectively) and increased IL6 concentration in the reference group only (23.5 ± 9.0%, p = 0.028).

Conclusion

In type 2 diabetic patients, the anti-inflammatory effect of rosiglitazone is not reflected by changes in NFκB and PPARγ target genes in PBMCs in vivo. Furthermore, our results do not support that high insulin concentrations contribute to the pro-inflammatory profile in type 2 diabetic patients.