Effect of insulin/PI3-K pathway on NO production in vitro
Abstract：Objective To elucidate the effect of insulin/phosphatidylinositol 3-kinase(PI3-K) sig-naling pathway on endothelial nitric oxide(NO) production. Methods The effects of insulin,glu-cose and wortmannin(inhibitor of PI3-K) on the PI3-K expression, the generation of NO and su-peroxide anion(O2-) in human umbilical vein endothelial cells(HUVECs) were investigated. The experiment included 9 groups, control group, 10 mU/L insulin, 100 mU/L insulin, mannitol, 5 mmol/L glucose+10 mU/L insulin,25 mmol/L glucose+ 100 mU/L insulin, 50 nmol/L wort-mannin, 50 nmol/L wortmannin+ 10 mU/L insulin and 50 nmol/L wortmannin+100 mU/L insu-lin. Results Different dosages of insulin(10 mU/L, 100 mU/L) significantly increased NO pro-duction and endothelial nitric oxide synthase(eNOS) activity in HUVECs as compared with con-trol group. In the presence of 25 mmol/L glucose+100 mU/L insulin,wortmannin and wortman-nin+insulin(10 mU/L, 100 mU/L), NO production and eNOS activity significantly decreased (P < 0.01 vs controls,respectively) accompanied by elevated O2- production (P < 0.01 vs con-trols, respectively). Compared with controls, insulin (10 mU/L, 100 mU/L)and wortmannin,wortmannin+insulin(10 mU/L,100 mU/L) promoted PI3-K expression. Conclusions PI3-K sig-naling pathway plays an important role in NO production and maintenance of endothelial func-tion. In insulin-resistant state, this pathway is damaged, leading to endothelial dysfunction.
Keywords：insulin1-phosphatidylinositol 3-kinasenitric oxideendothelial cellsnitric-oxide syn-thase
Publication Date：2009-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：4( 606-609 )