Authors: S Rome E Meugnier V Lecomte V Berbe J Besson C Cerutti S Pesenti A Granjon E Disse K Clement E Lefai M Laville H Vidal
Publish Date: 2009/07/10
Volume: 52, Issue: 9, Pages: 1899-1912
Abstract
One of the major processes by which insulin exerts its multiple biological actions is through gene expression regulation Thus the identification of transcription factors affected by insulin in target tissues represents an important challenge The aim of the present study was to gain a greater insight into this issue through the identification of transcription factor genes with insulinregulated expression in human skeletal muscleUsing microarray analysis we defined the sets of genes modulated during a 3 h hyperinsulinaemic–euglycaemic clamp 2 mU min−1 kg−1 in the skeletal muscle of insulinsensitive control volunteers and in moderately obese insulinresistant type 2 diabetic patientsOf the 1529 and 1499 genes regulated during the clamp in control and diabetic volunteers respectively we identified 30 transcription factors with impaired insulinregulation in type 2 diabetic patients Analysis of the promoters of the genes encoding these factors revealed a possible contribution of the transcriptional repressor basic helixloophelix domaincontaining class B 2 protein BHLHB2 insulin regulation of which is strongly altered in the muscle of diabetic patients Gene ontology analysis of BHLHB2 target genes identified after BHLHB2 overexpression in human primary myotubes demonstrated that about 10 of the genes regulated in vivo during hyperinsulinaemia are potentially under the control of this repressor The data also suggested that BHLHB2 is situated at the crossroads of a complex transcriptional network that is able to modulate major metabolic and biological pathways in skeletal muscle including the regulation of a cluster of genes involved in muscle development and contraction
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