Gene interactions and pathways from curated databases and text-mining
Am J Physiol Endocrinol Metab 2012, PMID: 22028412

Activation of mTOR/p70S6 kinase by ANG II inhibits insulin-stimulated endothelial nitric oxide synthase and vasodilation.

Kim, Jeong-A; Jang, Hyun-Ju; Martinez-Lemus, Luis A; Sowers, James R

Elevated tissue levels of angiotensin II (ANG II) are associated with impairment of insulin actions in metabolic and cardiovascular tissues. ANG II-stimulated activation of mammalian target of rapamycin (mTOR)/p70 S6 kinase (p70S6K) in cardiovascular tissues is implicated in cardiac hypertrophy and vascular remodeling. However, the role of ANG II-stimulated mTOR/p70S6K in vascular endothelium is poorly understood. In the present study, we observed that ANG II stimulated p70S6K in bovine aortic endothelial cells. ANG II increased phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser(636/639) and inhibited the insulin-stimulated phosphorylation of endothelial nitric oxide synthase (eNOS). An inhibitor of mTOR, rapamycin, attenuated the ANG II-stimulated phosphorylation of p70S6K and phosphorylation of IRS-1 (Ser(636/639)) and blocked the ability of ANG II to impair insulin-stimulated phosphorylation of eNOS, nitric oxide production, and mesenteric-arteriole vasodilation. Moreover, point mutations of IRS-1 at Ser(636/639) to Ala prevented the ANG II-mediated inhibition of insulin signaling. From these results, we conclude that activation of mTOR/p70S6K by ANG II in vascular endothelium may contribute to impairment of insulin-stimulated vasodilation through phosphorylation of IRS-1 at Ser(636/639). This ANG II-mediated impairment of vascular actions of insulin may help explain the role of ANG II as a link between insulin resistance and hypertension.

Document information provided by NCBI PubMed

Text Mining Data

nitric oxide synthase ⊣ ANG II: " Activation of mTOR/p70S6 kinase by ANG II inhibits insulin stimulated endothelial nitric oxide synthase and vasodilation "

nitric oxide synthase → insulin: " Activation of mTOR/p70S6 kinase by ANG II inhibits insulin stimulated endothelial nitric oxide synthase and vasodilation "

insulin receptor substrate-1 (IRS-1) ⊣ endothelial nitric oxide synthase (eNOS): " ANG II increased phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser ( 636/639 ) and inhibited the insulin stimulated phosphorylation of endothelial nitric oxide synthase (eNOS) "

endothelial nitric oxide synthase (eNOS) → insulin: " ANG II increased phosphorylation of insulin receptor substrate-1 (IRS-1) at Ser ( 636/639 ) and inhibited the insulin stimulated phosphorylation of endothelial nitric oxide synthase (eNOS) "

p70S6K → mTOR: " An inhibitor of mTOR , rapamycin, attenuated the ANG II-stimulated phosphorylation of p70S6K and phosphorylation of IRS-1 ( Ser ( 636/639 ) ) and blocked the ability of ANG II to impair insulin stimulated phosphorylation of eNOS, nitric oxide production, and mesenteric-arteriole vasodilation "

IRS-1 → mTOR: " An inhibitor of mTOR , rapamycin, attenuated the ANG II-stimulated phosphorylation of p70S6K and phosphorylation of IRS-1 ( Ser ( 636/639 ) ) and blocked the ability of ANG II to impair insulin stimulated phosphorylation of eNOS, nitric oxide production, and mesenteric-arteriole vasodilation "

eNOS → mTOR: " An inhibitor of mTOR , rapamycin, attenuated the ANG II-stimulated phosphorylation of p70S6K and phosphorylation of IRS-1 ( Ser ( 636/639 ) ) and blocked the ability of ANG II to impair insulin stimulated phosphorylation of eNOS , nitric oxide production, and mesenteric-arteriole vasodilation "

eNOS → insulin: " An inhibitor of mTOR, rapamycin, attenuated the ANG II-stimulated phosphorylation of p70S6K and phosphorylation of IRS-1 ( Ser ( 636/639 ) ) and blocked the ability of ANG II to impair insulin stimulated phosphorylation of eNOS , nitric oxide production, and mesenteric-arteriole vasodilation "

mTOR/p70S6K → ANG II: " From these results, we conclude that activation of mTOR/p70S6K by ANG II in vascular endothelium may contribute to impairment of insulin stimulated vasodilation through phosphorylation of IRS-1 at Ser ( 636/639 ) "

ANG II → mTOR/p70S6K: " From these results, we conclude that activation of mTOR/p70S6K by ANG II in vascular endothelium may contribute to impairment of insulin stimulated vasodilation through phosphorylation of IRS-1 at Ser ( 636/639 ) "

Manually curated Databases

No curated data.