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

• Main Authors: Mensink Marco, Plat Jogchum, Bragt Marjolijn CE, Schrauwen Patrick, Mensink Ronald P
• Format: Article
• Language: English
• Published: BMC 2009-02-01
• Series: BMC Endocrine Disorders
• Online Access: http://www.biomedcentral.com/1472-6823/9/8

<p>Abstract</p> <p>Background</p> <p>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 <it>in vivo</it>.</p> <p>Method</p> <p>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.</p> <p>Results</p> <p>Rosiglitazone reduced plasma MCP1 and hsCRP concentrations in diabetic patients (-9.5 ± 5.3 pg/mL, <it>p </it> = 0.043 and -1.1 ± 0.3 mg/L <it>p </it> = 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 (<it>p </it> < 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%, <it>p </it> = 0.001 and -11.1 ± 4.1%, <it>p </it> = 0.023, respectively) and increased IL6 concentration in the reference group only (23.5 ± 9.0%, <it>p </it> = 0.028).</p> <p>Conclusion</p> <p>In type 2 diabetic patients, the anti-inflammatory effect of rosiglitazone is not reflected by changes in NFκB and PPARγ target genes in PBMCs <it>in vivo</it>. Furthermore, our results do not support that high insulin concentrations contribute to the pro-inflammatory profile in type 2 diabetic patients.</p>