title: Moderate dose insulin promotes function of endothelial progenitor cells.
abstract: EPCs (endothelial progenitor cells) regenerate the vascular endothelial cells and keep the integrity of the vascular endothelium and thus may retard the onset of atherosclerosis. Steady state levels of EPCs in the circulation were found to be correlated with cardiovascular event risks. Given the close relationship between insulin and the cardiovascular system, we tested the long-term effects of moderate-dose insulin treatment on bone marrow-derived EPCs. Rat bone marrow EPCs were exposed to various levels of insulin under normal (5 mmol/l) or high (40 mmol/l) glucose conditions for 7 days. Insulin at levels near the physiological range (0.1, 1 nmol/l) up-regulated EPCs proliferation, stimulated NO (nitric oxide) production and reduced EPC senescence and ROS (reactive oxygen species) generation under both normal- and high-glucose conditions. Glucose exerted deleterious effects on EPCs contrary to insulin. Western blot analysis suggested concomitant decrease of Akt phosphorylation and eNOS (endothelial nitric oxide synthase) expression by high-glucose treatment and increase with insulin administration. Thus, insulin promoted several activities of EPCs, which suggested a potential endothelial protective role of insulin. Akt/eNOS pathway may be involved in the modulation of EPCs function by glucose and insulin.
authors.affiliation: Department of Cardiology, Xijing Hospital, The Fourth Military Medical University, Xian, Shaanxi, Peoples Republic of China.
authors.forename: Li
authors.initials: L
authors.lastname: Zhao
authors.forename: Feng
authors.initials: F
authors.lastname: Cao
authors.forename: Tao
authors.initials: T
authors.lastname: Yin
authors.forename: Dongdong
authors.initials: D
authors.lastname: Sun
authors.forename: Kang
authors.initials: K
authors.lastname: Cheng
authors.forename: Jun
authors.initials: J
authors.lastname: Zhang
authors.forename: Haichang
authors.initials: H
authors.lastname: Wang
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology; D049109:Cell Proliferation; D016922:Cellular Senescence; D042783:Endothelial Cells / Q000166:cytology*; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism* / Q000502:physiology
chemical_list: D007328:Insulin; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; D051057:Proto-Oncogene Proteins c-akt; D005947:Glucose