| pubmed-article:15964918 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C0044602 | lld:lifeskim |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C0285761 | lld:lifeskim |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C1368105 | lld:lifeskim |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C1451005 | lld:lifeskim |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C1705325 | lld:lifeskim |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C0225336 | lld:lifeskim |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C0037083 | lld:lifeskim |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C0020456 | lld:lifeskim |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C0277785 | lld:lifeskim |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C0334094 | lld:lifeskim |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C1150481 | lld:lifeskim |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C1710082 | lld:lifeskim |
| pubmed-article:15964918 | lifeskim:mentions | umls-concept:C0181586 | lld:lifeskim |
| pubmed-article:15964918 | pubmed:issue | 4 | lld:pubmed |
| pubmed-article:15964918 | pubmed:dateCreated | 2005-9-15 | lld:pubmed |
| pubmed-article:15964918 | pubmed:abstractText | Diabetes mellitus is a major risk factor for the development of vascular complications. We hypothesized that hyperglycemia decreases endothelial cell (EC) proliferation and survival via phosphatidylinositol 3-kinase (PI3k) and Akt signaling pathways. We cultured human umbilical vein ECs (HUVEC) in 5, 20, or 40 mM d-glucose. Cells grown in 5, 20, and 40 mM mannitol served as a control for osmotic effects. We measured EC proliferation for up to 15 days. We assessed apoptosis by annexin V and propidium iodide staining and flow cytometry, analyzed cell lysates obtained on culture day 8 for total and phosphorylated PI3k and Akt by Western blot analysis, and measured Akt kinase activity using a GSK fusion protein. HUVEC proliferation was also tested in the presence of pharmacological inhibitors of PI3k-Akt (wortmannin and LY294002) and after transfection with a constitutively active Akt mutant. ECs in media containing 5 mM d-glucose (control) exhibited log-phase growth on days 7-10. d-Glucose at 20 and 40 mM significantly decreased proliferation versus control (P < 0.05 for both), whereas mannitol did not impair EC proliferation. Apoptosis increased significantly in HUVEC exposed to 40 mM d-glucose. d-Glucose at 40 mM significantly decreased tyrosine-phosphorylated PI3k, threonine 308-phosphorylated-Akt, and Akt activity relative to control 5 mM d-glucose. Pharmacological inhibition of PI3k-Akt resulted in a dose-dependent decrease in EC proliferation. Transfection with a constitutively active Akt mutant protected ECs by enhancing proliferation when grown in 20 and 40 mM d-glucose. We conclude that d-glucose regulates Akt signaling through threonine phosphorylation of Akt and that hyperglycemia-impaired PI3k-Akt signaling may promote EC proliferative dysfunction in diabetes. | lld:pubmed |
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| pubmed-article:15964918 | pubmed:language | eng | lld:pubmed |
| pubmed-article:15964918 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:15964918 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:15964918 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
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| pubmed-article:15964918 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:15964918 | pubmed:month | Oct | lld:pubmed |
| pubmed-article:15964918 | pubmed:issn | 0363-6135 | lld:pubmed |
| pubmed-article:15964918 | pubmed:author | pubmed-author:HobsonRobert... | lld:pubmed |
| pubmed-article:15964918 | pubmed:author | pubmed-author:SaitoSatoshiS | lld:pubmed |
| pubmed-article:15964918 | pubmed:author | pubmed-author:VarmaShubhaS | lld:pubmed |
| pubmed-article:15964918 | pubmed:author | pubmed-author:BreslinJerome... | lld:pubmed |
| pubmed-article:15964918 | pubmed:author | pubmed-author:LalBrajesh... | lld:pubmed |
| pubmed-article:15964918 | pubmed:author | pubmed-author:PappasPeter... | lld:pubmed |
| pubmed-article:15964918 | pubmed:author | pubmed-author:DuránWalter... | lld:pubmed |
| pubmed-article:15964918 | pubmed:author | pubmed-author:ZhengRuifangR | lld:pubmed |
| pubmed-article:15964918 | pubmed:issnType | Print | lld:pubmed |
| pubmed-article:15964918 | pubmed:volume | 289 | lld:pubmed |
| pubmed-article:15964918 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:15964918 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:15964918 | pubmed:pagination | H1744-51 | lld:pubmed |
| pubmed-article:15964918 | pubmed:dateRevised | 2011-5-12 | lld:pubmed |
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| pubmed-article:15964918 | pubmed:meshHeading | pubmed-meshheading:15964918... | lld:pubmed |
| pubmed-article:15964918 | pubmed:year | 2005 | lld:pubmed |
| pubmed-article:15964918 | pubmed:articleTitle | Hyperglycemia alters PI3k and Akt signaling and leads to endothelial cell proliferative dysfunction. | lld:pubmed |
