Linked Life Data

17210752

Source:http://linkedlifedata.com/resource/pubmed/id/17210752

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-1-9
pubmed:abstractText
Signaling pathways of IGF-I and insulin receptors play important roles in the regulation of myocardial function. FOXO1 is a member of the forkhead transcriptional factor family, but how insulin and IGF-I receptor signaling regulate FOXO1 in cardiomyocytes is not well understood. This study was carried out to elucidate how IGF-I and insulin receptor signaling modulate FOXO1 in cardiomyocytes. In cardiomyocytes, activation of IGF-I receptor and insulin receptor lead to rapid phosphorylation of FOXO1. Inhibition of phosphatidylinositol 3-kinase/Akt pathway suppressed the effect of insulin and IGF-I on FOXO1 phosphorylation. Prolonged incubation with IGF-I increased ubiquitination of FOXO1 and down-regulated the abundance of FOXO1 proteins, which suggested that IGF-I might modulate FOXO1 degradation. To explore whether FOXO1 could modulate IGF-I and insulin signaling, a constitutively active FOXO1 was overexpressed in cardiomyocytes. The abundance of insulin receptor and IGF-I receptor was significantly upregulated in the cells overexpressing active FOXO1, accompanied by increased receptor phosphorylation upon insulin/IGF-I stimulation. Interestingly, overexpression of constitutively active FOXO1 also led to activation of MEK and Akt phosphorylation. IGF-I-stimulated MEK and Akt phosphorylation were augmented byoverexpression of constitutively active FOXO1. These findings indicate bidirectional regulation of insulin/IGF-I receptor signaling and FOXO1 in cardiomyocytes. FOXO1 may provide feedback control through upregulation of insulin and IGF-I receptor signaling.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0022-0795
pubmed:author
pubmed:issnType
Print
pubmed:volume
192
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
149-58
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:17210752-Adenoviridae, pubmed-meshheading:17210752-Animals, pubmed-meshheading:17210752-Animals, Newborn, pubmed-meshheading:17210752-Cells, Cultured, pubmed-meshheading:17210752-Forkhead Transcription Factors, pubmed-meshheading:17210752-Gene Expression Regulation, pubmed-meshheading:17210752-Genetic Vectors, pubmed-meshheading:17210752-Immunoblotting, pubmed-meshheading:17210752-Immunoprecipitation, pubmed-meshheading:17210752-Insulin-Like Growth Factor I, pubmed-meshheading:17210752-MAP Kinase Kinase 1, pubmed-meshheading:17210752-Myocytes, Cardiac, pubmed-meshheading:17210752-Nerve Tissue Proteins, pubmed-meshheading:17210752-Oncogene Protein v-akt, pubmed-meshheading:17210752-Phosphorylation, pubmed-meshheading:17210752-Rats, pubmed-meshheading:17210752-Rats, Sprague-Dawley, pubmed-meshheading:17210752-Receptor, IGF Type 1, pubmed-meshheading:17210752-Receptor, Insulin, pubmed-meshheading:17210752-Signal Transduction, pubmed-meshheading:17210752-Transduction, Genetic
pubmed:year
2007
pubmed:articleTitle
Bidirectional regulation of upstream IGF-I/insulin receptor signaling and downstream FOXO1 in cardiomyocytes.
pubmed:affiliation
Department of Medicine, Biological Chemistry, Physiology and Biophysics, Center for Diabetes Research and Treatment, University of California, Irvine, CA 92697, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural