title: The transcriptional response in human umbilical vein endothelial cells exposed to insulin: a dynamic gene expression approach.
abstract: BACKGROUND
  In diabetes chronic hyperinsulinemia contributes to the instability of the atherosclerotic plaque and stimulates cellular proliferation through the activation of the MAP kinases, which in turn regulate cellular proliferation. However, it is not known whether insulin itself could increase the transcription of specific genes for cellular proliferation in the endothelium. Hence, the characterization of transcriptional modifications in endothelium is an important step for a better understanding of the mechanism of insulin action and the relationship between endothelial cell dysfunction and insulin resistance.
  
  
  RESULTS
  The transcriptional response of endothelial cells in the 440 minutes following insulin stimulation was monitored using microarrays and compared to a control condition. About 1700 genes were selected as differentially expressed based on their treated minus control profile, thus allowing the detection of even small but systematic changes in gene expression. Genes were clustered in 7 groups according to their time expression profile and classified into 15 functional categories that can support the biological effects of insulin, based on Gene Ontology enrichment analysis. In terms of endothelial function, the most prominent processes affected were NADH dehydrogenase activity, N-terminal myristoylation domain binding, nitric-oxide synthase regulator activity and growth factor binding. Pathway-based enrichment analysis revealed "Electron Transport Chain" significantly enriched. Results were validated on genes belonging to "Electron Transport Chain" pathway, using quantitative RT-PCR.
  
  
  CONCLUSIONS
  As far as we know, this is the first systematic study in the literature monitoring transcriptional response to insulin in endothelial cells, in a time series microarray experiment. Since chronic hyperinsulinemia contributes to the instability of the atherosclerotic plaque and stimulates cellular proliferation, some of the genes identified in the present work are potential novel candidates in diabetes complications related to endothelial dysfunction.
authors.affiliation: Information Engineering Department, University of Padova, Padova, Italy.
authors.forename: Barbara
authors.initials: B
authors.lastname: Di Camillo
authors.forename: Tiziana
authors.initials: T
authors.lastname: Sanavia
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Iori
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bronte
authors.forename: Enrica
authors.initials: E
authors.lastname: Roncaglia
authors.forename: Alberto
authors.initials: A
authors.lastname: Maran
authors.forename: Angelo
authors.initials: A
authors.lastname: Avogaro
authors.forename: Gianna
authors.initials: G
authors.lastname: Toffolo
authors.forename: Claudio
authors.initials: C
authors.lastname: Cobelli
mesh_terms: D050197:Atherosclerosis / Q000378:metabolism; D049109:Cell Proliferation; D003920:Diabetes Mellitus / Q000378:metabolism; D004579:Electron Transport; D042783:Endothelial Cells / Q000166:cytology*; D004730:Endothelium, Vascular / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D020935:MAP Kinase Signaling System; D014158:Transcription, Genetic; D014471:Umbilical Veins / Q000166:cytology* / Q000378:metabolism
chemical_list: D007328:Insulin