IL-1 receptor antagonism and muscle gene expression in patients with type 2 diabetes
IL-1 receptor antagonism and muscle gene expression in patients with type 2 diabetes
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DOI：
10.1684/ecn.2009.0152
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发表时间：
2009-01-01
影响因子：
2.8
通讯作者：
Mandrup-Poulsen, Thomas
中科院分区：
文献类型：
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作者：
Berchtold, Lukas A.;Larsen, Claus M.;Mandrup-Poulsen, Thomas
背景我们以前曾报道过，在2型糖尿病患者中使用阿那白滞素（一种重组人白介素-1受体拮抗剂，IL-1Ra）全身阻断IL-1 β，降低糖化血红蛋白，改善β细胞功能，降低IL-6和CRP的循环水平（7）。为了研究IL-1Ra在胰岛素敏感组织中的作用，分析了用IL-1Ra治疗的2型糖尿病患者骨骼肌中的基因表达水平。方法.使用Affytron U133Plus2.0基因芯片，在IL-1Ra（阿那白滞素）治疗13周之前和之后，测定了5名肥胖患者（BMI> 27）股外侧肌活检组织中的基因表达谱。使用四种不同的算法：RMA、GCRMA、dChip和GCOS对微阵列数据进行归一化和独立分析。对每个基因的微阵列数据进行假设检验，并使用蛋白质网络分析来识别受治疗影响的生物网络/途径。通过qRT-PCR测定安慰剂治疗患者（n = 12）和阿那白滞素治疗患者（n = 11）肌肉中候选基因（COL1A1、CDKN1C、HSP 70、HLA-A、IL-1和IL-6）的基因表达水平。结果在IL-1Ra处理后被鉴定为显著调节的转录物的变化的一致性较低。在错误发现率校正后，未证明表达水平显著改变。蛋白质相互作用网络未显示任何改变的网络/途径。当比较每个个体治疗前后的转录本数量时，通过qRT-PCR定量的候选基因均未发生显著改变。结论IL-1Ra治疗并没有显着影响骨骼肌中的基因表达水平，在这个有限的和选定的样本肥胖2型糖尿病患者。更大规模的研究可能会证实阿那白滞素对肌肉组织基因表达缺乏影响。
Background. We have previously reported that systemic blockade of IL-1 beta in patients with type 2 diabetes with anakinra (a recombinant human interleukin-1-receptor antagonist, IL-1Ra), lowered glycated hemoglobin improved beta-cell function and reduced circulating levels of IL-6 and CRP (7). To investigate the effects of IL-1Ra in insulin-sensitive tissue, gene expression levels in skeletal muscle from type 2 diabetic patients treated with IL-1Ra were analysed. Methods. Gene expression profiles in vastus lateralis muscle biopsies from five obese patients (BMI>27) were determined before and after 13 weeks of treatment with IL-1Ra (anakinra) using Affymetrix U133Plus2.0 GeneChips. Microarray data were normalized and analysed independently using four different algorithms; RMA, GCRMA, dChip and GCOS. Hypothesis tests were applied to the microarray data for each gene, and protein network analysis was used to identify biological networks/pathways affected by the treatment. Gene expression levels for candidate genes (COL1A1, CDKN1C, HSP70, HLA-A, IL-1 and IL-6) were determined by qRT-PCR in muscles of placebo- (n=12) and anakinra-treated patients (n=11). Results. The concordance of the variations of the transcripts identified as significantly regulated after IL-1Ra treatment was low. No significantly altered expression levels could be demonstrated after false discovery rate correction. The protein interaction network did not reveal any altered networks/pathways. None of the candidate genes, quantified by qRT-PCR, were significantly altered when comparing the number of transcripts before and after treatment for each individual. Conclusion. Treatment with IL-1Ra did not significantly affect gene expression levels in skeletal muscle in this limited and selected sample of obese patients with type 2 diabetes. Larger studies might confirm the lack of effect of anakinra on muscle tissue gene expression.