title: Vascular insulin resistance related to endoplasmic reticulum stress in aortas from a rat model of chronic kidney disease.
abstract: Metabolic insulin resistance has been demonstrated in patients with nondiabetic chronic kidney disease (CKD), yet their vascular insulin signaling remains poorly understood. Here we tested the hypothesis that vascular insulin signaling was impaired and related with endoplasmic reticulum (ER) stress in aortas from the reduced renal mass (RRM) model of CKD. The activity of insulin signaling and markers of ER were determined in aortas from rats with RRM and cultured human umbilical vein endothelial cells. Tyrosine phosphorylation of insulin receptor-β and insulin receptor substrate (IRS)-1 and phosphorylation of protein kinase B and endothelial nitric oxide synthase were all decreased in aorta from RRM rats, whereas serine phosphorylation of IRS-1, a marker of insulin resistance, was increased. In addition, nitric oxide generation and insulin-mediated vasorelaxation were decreased in aortas from RRM rats. Insulin signaling in cultured vascular endothelial cells was impaired by induction of ER stress and was restored in aortas of RRM rats by inhibition of ER stress. Taken together, rats with RRM had vascular insulin resistance that was linked to ER stress. This identified vascular insulin resistance and ER stress as a potential therapeutic target for cardiovascular complications in patients with CKD.
authors.affiliation: Division of Nephrology, Nanfang Hospital, Southern Medical University, Key Lab for Organ Failure Research, Ministry of Education, Guangzhou, China.
authors.forename: Qiu Gen
authors.initials: QG
authors.lastname: Zhou
authors.forename: Xiao Jing
authors.initials: XJ
authors.lastname: Fu
authors.forename: Guo Yu
authors.initials: GY
authors.lastname: Xu
authors.forename: Wei
authors.initials: W
authors.lastname: Cao
authors.forename: Hong Fa
authors.initials: HF
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Nie
authors.forename: Min
authors.initials: M
authors.lastname: Liang
authors.forename: Fan Fan
authors.initials: FF
authors.lastname: Hou
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004721:Endoplasmic Reticulum / Q000502:physiology*; D059865:Endoplasmic Reticulum Stress / Q000502:physiology*; D004730:Endothelium, Vascular / Q000166:cytology / Q000378:metabolism; D006801:Humans; D055504:Insulin Receptor Substrate Proteins / Q000378:metabolism; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011972:Receptor, Insulin / Q000378:metabolism; D051436:Renal Insufficiency, Chronic / Q000503:physiopathology*; D015398:Signal Transduction / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology*
chemical_list: D055504:Insulin Receptor Substrate Proteins; D011972:Receptor, Insulin; D051057:Proto-Oncogene Proteins c-akt