Defective insulin and acetylcholine induction of endothelial cell-nitric oxide synthase through insulin receptor substrate/Akt signaling pathway in aorta of obese rats

dc.creatorZecchin, HG
dc.creatorPriviero, FBM
dc.creatorSouza, CT
dc.creatorZecchin, KG
dc.creatorPrada, PO
dc.creatorCarvalheira, JBC
dc.creatorVelloso, LA
dc.creatorAntunes, E
dc.creatorSaad, MJA
dc.date2007
dc.dateAPR
dc.date2014-11-15T22:53:43Z
dc.date2015-11-26T17:22:19Z
dc.date2014-11-15T22:53:43Z
dc.date2015-11-26T17:22:19Z
dc.date.accessioned2018-03-29T00:09:47Z
dc.date.available2018-03-29T00:09:47Z
dc.identifierDiabetes. Amer Diabetes Assoc, v. 56, n. 4, n. 1014, n. 1024, 2007.
dc.identifier0012-1797
dc.identifierWOS:000245697200014
dc.identifier10.2337/db05-1147
dc.identifierhttp://www.repositorio.unicamp.br/jspui/handle/REPOSIP/79367
dc.identifierhttp://www.repositorio.unicamp.br/handle/REPOSIP/79367
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/79367
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1283580
dc.descriptionThe actions of acetylcholine (ACh) on endothelium mainly are mediated through muscarinic receptors, which are members of the G protein-coupled receptor family. In the present study, we show that ACh induces rapid tyrosine phosphorylation and activation of Janus kinase 2 (JAK2) in rat aorta. Upon JAK2 activation, tyrosine phosphorylation of insulin receptor substrate (IRS)-1 is detected. In addition, ACh induces JAK2/IRS-1 and IRS-1/phosphatidylinositol (PI) 3-kinase associations, downstream activation of Akt/protein kinase B, endothelial cell-nitric oxide synthase (eNOS), and extracellular signal-regulated kinase (ERK)-1/2. The pharmacological blockade of JAK2 or PI 3-kinase reduced ACh-stimulated eNOS phosphorylation, NOS activity, and aorta relaxation. These data indicate a new signal transduction pathway for IRS-1/PI 3-kinase/Akt/eNOS activation and ERK1/2 by means of JAK2 tyrosine phosphorylation stimulated by ACh in vessels. Moreover, we demonstrate that in aorta of obese rats (high-fat diet), there is an impairment in the insulin- and ACh-stimulated IRS-1/PI 3-kinase pathway, leading to reduced activation with lower protein levels of eNOS associated with a hyperactivated ERK/mitogen-activated protein kinase pathway. These results suggest that in aorta of obese rats, there not only is insulin resistance but also ACh resistance, probably mediated by a common signaling pathway that controls the activity and the protein levels of eNOS.
dc.description56
dc.description4
dc.description1014
dc.description1024
dc.languageen
dc.publisherAmer Diabetes Assoc
dc.publisherAlexandria
dc.publisherEUA
dc.relationDiabetes
dc.relationDiabetes
dc.rightsfechado
dc.sourceWeb of Science
dc.subjectSmooth-muscle-cells
dc.subjectGrowth-factor-i
dc.subjectTyrosine Phosphorylation
dc.subjectAngiotensin-ii
dc.subjectPhosphatidylinositol 3-kinase
dc.subjectMesangial Cells
dc.subjectKinase-activity
dc.subjectResistance
dc.subjectActivation
dc.subjectExpression
dc.titleDefective insulin and acetylcholine induction of endothelial cell-nitric oxide synthase through insulin receptor substrate/Akt signaling pathway in aorta of obese rats
dc.typeArtículos de revistas


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