罗格列酮的抗炎作用在2型糖尿病患者外周血单个核细胞中NFκB相关基因的表达上未得到体现。

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

作者信息

Bragt Marjolijn C E, Plat Jogchum, Mensink Marco, Schrauwen Patrick, Mensink Ronald P

机构信息

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

出版信息

BMC Endocr Disord. 2009 Feb 25;9:8. doi: 10.1186/1472-6823-9-8.

DOI:10.1186/1472-6823-9-8

PMID:19243600

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC2653037/

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 x 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 NFkappaB-related genes and PPARgamma target genes in PBMCs, plasma TNFalpha, 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 NFkappaB-related genes that were measured in PBMCs from type 2 diabetic subjects, only RELA, SLC20A1, INFgamma and IL1R1 changed significantly (p < 0.05). In addition, PPARgamma 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 NFkappaB and PPARgamma 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.

摘要

背景

罗格列酮不仅能改善胰岛素敏感性，还具有抗炎作用。我们现已在2型糖尿病患者中研究这些作用是否通过外周血单核细胞（PBMCs）中mRNA表达的变化得以体现，以确定这些细胞能否用于在体内分子水平研究这些抗炎作用。

方法

11名肥胖的2型糖尿病患者接受罗格列酮治疗（2×4mg/d），为期8周。在治疗前后采集空腹血样。10名肥胖对照受试者作为参照组。检测PBMCs中NFκB相关基因和PPARγ靶基因的表达、血浆肿瘤坏死因子α（TNFα）、白细胞介素6（IL6）、单核细胞趋化蛋白1（MCP1）和超敏C反应蛋白（hsCRP）的浓度。此外，在高胰岛素-正常血糖钳夹试验后采集血样。

结果

罗格列酮降低了糖尿病患者血浆MCP1和hsCRP的浓度（分别为-9.5±5.3pg/mL，p=0.043；-1.1±0.3mg/L，p=0.003）。就hsCRP而言，其浓度与非糖尿病参照组相当。然而，在对2型糖尿病受试者PBMCs中检测的84个NFκB相关基因中，只有RELA、溶质载体家族20成员1（SLC20A1）、干扰素γ（INFγ）和白细胞介素1受体1（IL1R1）有显著变化（p<0.05）。此外，PPARγ及其靶基因（CD36和脂蛋白脂肪酶（LPL））没有变化。在钳夹试验期间，胰岛素降低了糖尿病组和参照组血浆MCP1的浓度（分别为-9.1±1.8%，p=0.001；-11.1±4.1%，p=0.023），且仅使参照组的IL6浓度升高（23.5±9.0%，p=0.028）。