Open Access

ARTICLE

IL-1 receptor antagonism and muscle gene expression in patients with type 2 diabetes

Lukas A. Berchtold^1,2, Claus M. Larsen², Allan Vaag², Mirjam Faulenbach³, Christopher T. Workman⁴, Mogens Kruhøffer⁵, Marc Donath³, Thomas Mandrup-Poulsen^1,2,6

1 Hagedorn Research Institute, Gentofte, Denmark
2 Steno Diabetes Center, Gentofte, Denmark
3 Clinic for Endocrinology and Diabetes, University Hospital Zurich, Switzerland
4 Center for Biological Sequence Analysis, Department of Systems Biology, Technical University of Denmark, Denmark
5 Molecular Diagnostic Laboratory, Department of Clinical Biochemistry, Aarhus University Hospital Skejby, Denmark
6 Core Unit for Medical Research Methodology, Department of Biomedical Sciences, University of Copenhagen, Denmark

* Corresponding Author: T. Mandrup-Poulsen,

European Cytokine Network 2009, 20(2), 81-87. https://doi.org/10.1684/ecn.2009.0152

Accepted 26 January 2009;

Abstract

Background. We have previously reported that systemic blockade of IL-1β 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 biop-sies 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 indepen-dently 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 can-didate 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 diabe-tes. Larger studies might confirm the lack of effect of anakinra on muscle tissue gene expression.

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