Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

Vascular insulin resistance related to endoplasmic reticulum stress in aortas from a rat model of chronic kidney disease.

Authors: Zhou, QG  Fu, XJ  Xu, GY  Cao, W  Liu, HF  Nie, J  Liang, M  Hou, FF 
Citation: Zhou QG, etal., Am J Physiol Heart Circ Physiol. 2012 Nov 1;303(9):H1154-65. doi: 10.1152/ajpheart.00407.2012. Epub 2012 Aug 31.
Pubmed: (View Article at PubMed) PMID:22942179
DOI: Full-text: DOI:10.1152/ajpheart.00407.2012

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-beta 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.

Annotation

Disease Annotations
Objects Annotated

Additional Information

 
RGD Object Information
RGD ID: 7207055
Created: 2013-01-17
Species: All species
Last Modified: 2013-01-17
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.