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The transcriptional response in human umbilical vein endothelial cells exposed to insulin: a dynamic gene expression approach.

Di Camillo B, Sanavia T, Iori E, Bronte V, Roncaglia E, Maran A, Avogaro A, Toffolo G, Cobelli C - PLoS ONE (2010)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Information Engineering Department, University of Padova, Padova, Italy.

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.

Methodology and principal findings: 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.

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Related in: MedlinePlus

GO graph of enriched molecular function terms.The paths of GO enriched terms are displayed; nodes directly connected by a path in the GO graph were grouped together into 15 GO main annotation groups (denoted by capital letters).
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pone-0014390-g002: GO graph of enriched molecular function terms.The paths of GO enriched terms are displayed; nodes directly connected by a path in the GO graph were grouped together into 15 GO main annotation groups (denoted by capital letters).

Mentions: The GO sub-graph containing all the paths from the 26 enriched GO terms to the root is depicted in Figure 2, where enriched GO terms are grouped together into 15 main GO groups, according to the rules explained in Methods; namely, Protein binding, Actin binding, N-terminal myristoylation domain binding, Nitric-oxide synthase regulator activity, RNA binding, Structure-specific DNA binding, Translation initiation factor activity, Transcription corepressor activity, NADH dehydrogenase activity, 1-phosphatidylinositol-3-kinase activity, RNA polymerase subunit kinase activity, Protein geranylgeranyltransferase activity, Cis-trans isomerase activity, Hydrolase activity, Protein transporter activity. Ten out of fifteen groups correspond to isolated nodes in the GO database.


The transcriptional response in human umbilical vein endothelial cells exposed to insulin: a dynamic gene expression approach.

Di Camillo B, Sanavia T, Iori E, Bronte V, Roncaglia E, Maran A, Avogaro A, Toffolo G, Cobelli C - PLoS ONE (2010)

GO graph of enriched molecular function terms.The paths of GO enriched terms are displayed; nodes directly connected by a path in the GO graph were grouped together into 15 GO main annotation groups (denoted by capital letters).
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3008714&req=5

pone-0014390-g002: GO graph of enriched molecular function terms.The paths of GO enriched terms are displayed; nodes directly connected by a path in the GO graph were grouped together into 15 GO main annotation groups (denoted by capital letters).
Mentions: The GO sub-graph containing all the paths from the 26 enriched GO terms to the root is depicted in Figure 2, where enriched GO terms are grouped together into 15 main GO groups, according to the rules explained in Methods; namely, Protein binding, Actin binding, N-terminal myristoylation domain binding, Nitric-oxide synthase regulator activity, RNA binding, Structure-specific DNA binding, Translation initiation factor activity, Transcription corepressor activity, NADH dehydrogenase activity, 1-phosphatidylinositol-3-kinase activity, RNA polymerase subunit kinase activity, Protein geranylgeranyltransferase activity, Cis-trans isomerase activity, Hydrolase activity, Protein transporter activity. Ten out of fifteen groups correspond to isolated nodes in the GO database.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Information Engineering Department, University of Padova, Padova, Italy.

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.

Methodology and principal findings: 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.

Show MeSH
Related in: MedlinePlus