@Article{ecn.2009.0152,
AUTHOR = {Lukas A. Berchtold, Claus M. Larsen, Allan Vaag, Mirjam Faulenbach, Christopher T. Workman, Mogens Kruhøffer, Marc Donath, Thomas Mandrup-Poulsen},
TITLE = {IL-1 receptor antagonism and muscle gene expression in patients with type 2 diabetes},
JOURNAL = {European Cytokine Network},
VOLUME = {20},
YEAR = {2009},
NUMBER = {2},
PAGES = {81--87},
URL = {http://www.techscience.com/ECN/v20n2/65907},
ISSN = {1952-4005},
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.},
DOI = {10.1684/ecn.2009.0152}
}