Linked Life Data

21357660

Source:http://linkedlifedata.com/resource/pubmed/id/21357660

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-5-17
pubmed:abstractText
The elderly are prone to postprandial hyperglycemia that increases their cardiovascular risk. Although insulin therapy is necessary to treat diabetes, high plasma concentrations of insulin may cause the development of atherosclerosis and accelerate endothelial senescence. We assumed that high glucose causes stress-induced premature senescence and replicative senescence and examined the regulatory role of insulin in endothelial senescence and functions under different glucose conditions. Exposure of human endothelial cells to high glucose (22 mM) for 3 days increased senescence-associated-?-galactosidase activity, a senescence marker, and decreased telomerase activity, a replicative senescence marker. Physiological concentrations of insulin preserved telomere length and delayed endothelial senescence under high-glucose conditions. The effect of insulin under high-glucose conditions was associated with reduced reactive oxygen species and increased nitric oxide (NO). Small interfering RNA targeting endothelial NO synthase reduced the antisenescence effects of insulin. Physiological concentrations of insulin also reversed high glucose-induced increases in p53 and vascular cell adhesion molecule-1 and decreases in senescence marker protein-30. On the other hand, when insulin was given at any concentrations under normal glucose or at high concentrations under high glucose, its ability to promote cellular senescence was unrelated to endothelial NO. Finally, streptozotocin-induced diabetes showed more senescent cells in the aortic endothelium of aged rats compared with age-matched control and insulin-treated animals. Conclusively, the regulatory effects of insulin on endothelial senescence were modulated by the glucose environment. These data may help explain insulin's complicated roles in atherosclerosis in the elderly.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1521-0103
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
337
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
591-9
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed-meshheading:21357660-Aging, pubmed-meshheading:21357660-Animals, pubmed-meshheading:21357660-Aorta, pubmed-meshheading:21357660-Atherosclerosis, pubmed-meshheading:21357660-Cell Aging, pubmed-meshheading:21357660-Cells, Cultured, pubmed-meshheading:21357660-Diabetes Mellitus, Experimental, pubmed-meshheading:21357660-Dose-Response Relationship, Drug, pubmed-meshheading:21357660-Endothelial Cells, pubmed-meshheading:21357660-Endothelium, Vascular, pubmed-meshheading:21357660-Glucose, pubmed-meshheading:21357660-Humans, pubmed-meshheading:21357660-Hypoglycemic Agents, pubmed-meshheading:21357660-Insulin, pubmed-meshheading:21357660-Nitric Oxide, pubmed-meshheading:21357660-Nitric Oxide Synthase Type III, pubmed-meshheading:21357660-RNA, Small Interfering, pubmed-meshheading:21357660-Rats, pubmed-meshheading:21357660-Telomerase, pubmed-meshheading:21357660-Telomere, pubmed-meshheading:21357660-Umbilical Veins, pubmed-meshheading:21357660-beta-Galactosidase
pubmed:year
2011
pubmed:articleTitle
Dose-dependent modulatory effects of insulin on glucose-induced endothelial senescence in vitro and in vivo: a relationship between telomeres and nitric oxide.
pubmed:affiliation
Department of Geriatrics, Nagoya University Graduate School of Medicine, Nagoya 466-8550, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't