Linked Life Data

16253633

Source:http://linkedlifedata.com/resource/pubmed/id/16253633

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2005-10-28
pubmed:abstractText
Diabetes mellitus results in chronic hyperglycemia, a serious metabolic disorder associated with a markedly increased risk of cardiovascular disease. However, the effects of high glucose (HG) on cardiac myocyte growth have not been fully clarified. In this study, the effect of glucose on cardiac myocyte growth was examined using leucine incorporation as an index of protein synthesis. High glucose (HG, 25 mmol/L) increased leucine incorporation (167% +/- 0.2% over normal glucose, n=4, P<.01) compared with a physiological glucose concentration (5.5 mmol/L, normal glucose). The HG-induced increase in leucine incorporation was time- and dose-dependent and was not due to osmotic changes because 25 mmol/L mannitol did not change leucine incorporation. High glucose also significantly reduced elongation factor 2 phosphorylation, an effect known to result in increased protein synthesis at the elongation step. Western blot analysis showed that HG-activated protein kinase B (PKB), also called Akt (PKB/Akt), at 18 hours. High glucose-induced leucine incorporation was attenuated with phosphatidylinositol 3-kinase (PI3K) inhibition using wortmannin and LY294002 and by rapamycin, a mammalian target of rapamycin (mTOR) inhibitor, 72%, 64%, and 65% (P<.05), respectively. High glucose also activated extracellular signal-regulated kinase 1/2 activity with peak stimulation at 5 minutes. In addition, PD98059, an inhibitor of mitogen-activated protein kinase kinase, attenuated HG-induced leucine incorporation. These data show for the first time that elevated glucose increases protein synthesis in cardiac myocytes. The increase appears to be mediated by activation of PI3K-PKB/Akt and/or PI3K-mTOR as well as extracellular signal-regulated kinase 1/2. These results provide new evidence for a direct effect of glucose independent of insulin on cardiac myocyte growth.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0026-0495
pubmed:author
pubmed:issnType
Print
pubmed:volume
54
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1453-60
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:16253633-Animals, pubmed-meshheading:16253633-Antibiotics, Antineoplastic, pubmed-meshheading:16253633-Cells, Cultured, pubmed-meshheading:16253633-Glucose, pubmed-meshheading:16253633-Leucine, pubmed-meshheading:16253633-Mitogen-Activated Protein Kinase 1, pubmed-meshheading:16253633-Mitogen-Activated Protein Kinase 3, pubmed-meshheading:16253633-Myocytes, Cardiac, pubmed-meshheading:16253633-Peptide Elongation Factor 2, pubmed-meshheading:16253633-Phosphorylation, pubmed-meshheading:16253633-Protein Biosynthesis, pubmed-meshheading:16253633-Proto-Oncogene Proteins c-akt, pubmed-meshheading:16253633-Rats, pubmed-meshheading:16253633-Rats, Sprague-Dawley, pubmed-meshheading:16253633-Ribosomal Protein S6 Kinases, 70-kDa, pubmed-meshheading:16253633-Signal Transduction, pubmed-meshheading:16253633-Sirolimus
pubmed:year
2005
pubmed:articleTitle
Elevated glucose activates protein synthesis in cultured cardiac myocytes.
pubmed:affiliation
Division of Endocrinology and Metabolism, Department of Internal Medicine, University of Virginia Health Science Center, Charlottesville, VA 22908, USA. yw4w@virginia.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural